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PMC:1283364 / 48153-62158 JSONTXT 5 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T10541 11-13 PRP denotes We
T10542 14-21 VBP denotes present
T10543 22-23 DT denotes a
T10545 24-27 JJ denotes new
T10546 28-33 NN denotes mouse
T10544 34-39 NN denotes model
T10547 40-43 IN denotes for
T10548 44-46 NN denotes AD
T10549 47-51 WDT denotes that
T10551 52-55 VBD denotes was
T10550 56-64 VBN denotes designed
T10552 65-67 TO denotes to
T10553 68-72 VB denotes test
T10554 73-76 DT denotes the
T10555 77-89 NNS denotes consequences
T10556 90-92 IN denotes of
T10557 93-103 VBG denotes inhibiting
T10558 104-106 NN denotes Aβ
T10559 107-117 NN denotes production
T10560 118-123 IN denotes after
T10561 124-127 DT denotes the
T10562 128-133 NN denotes onset
T10563 134-136 IN denotes of
T10564 137-144 NN denotes amyloid
T10565 145-154 NN denotes pathology
T10566 154-155 . denotes .
T10567 155-310 sentence denotes New lines of transgenic mice were developed for this study that express high levels of APPswe/ind under the control of a tetracycline-responsive promoter.
T10568 156-159 JJ denotes New
T10569 160-165 NNS denotes lines
T10571 166-168 IN denotes of
T10572 169-179 JJ denotes transgenic
T10573 180-184 NNS denotes mice
T10574 185-189 VBD denotes were
T10570 190-199 VBN denotes developed
T10575 200-203 IN denotes for
T10576 204-208 DT denotes this
T10577 209-214 NN denotes study
T10578 215-219 WDT denotes that
T10579 220-227 VBP denotes express
T10580 228-232 JJ denotes high
T10581 233-239 NNS denotes levels
T10582 240-242 IN denotes of
T10583 243-249 NN denotes APPswe
T10585 249-250 HYPH denotes /
T10584 250-253 NN denotes ind
T10586 254-259 IN denotes under
T10587 260-263 DT denotes the
T10588 264-271 NN denotes control
T10589 272-274 IN denotes of
T10590 275-276 DT denotes a
T10592 277-289 NN denotes tetracycline
T10594 289-290 HYPH denotes -
T10593 290-300 JJ denotes responsive
T10591 301-309 NN denotes promoter
T10595 309-310 . denotes .
T10596 310-508 sentence denotes We demonstrate that treatment with dox suppresses steady-state levels of both APPswe/ind and its C-terminal fragments, indicating that the mutant proteins have a relatively short half-life in vivo.
T10597 311-313 PRP denotes We
T10598 314-325 VBP denotes demonstrate
T10599 326-330 IN denotes that
T10601 331-340 NN denotes treatment
T10602 341-345 IN denotes with
T10603 346-349 NN denotes dox
T10600 350-360 VBZ denotes suppresses
T10604 361-367 JJ denotes steady
T10606 367-368 HYPH denotes -
T10605 368-373 NN denotes state
T10607 374-380 NNS denotes levels
T10608 381-383 IN denotes of
T10609 384-388 CC denotes both
T10611 389-395 NN denotes APPswe
T10612 395-396 HYPH denotes /
T10610 396-399 NN denotes ind
T10613 400-403 CC denotes and
T10614 404-407 PRP$ denotes its
T10616 408-409 NN denotes C
T10617 409-410 HYPH denotes -
T10618 410-418 JJ denotes terminal
T10615 419-428 NNS denotes fragments
T10619 428-430 , denotes ,
T10620 430-440 VBG denotes indicating
T10621 441-445 IN denotes that
T10623 446-449 DT denotes the
T10625 450-456 NN denotes mutant
T10624 457-465 NN denotes proteins
T10622 466-470 VBP denotes have
T10626 471-472 DT denotes a
T10628 473-483 RB denotes relatively
T10629 484-489 JJ denotes short
T10630 490-494 NN denotes half
T10631 494-495 HYPH denotes -
T10627 495-499 NN denotes life
T10632 500-502 FW denotes in
T10633 503-507 FW denotes vivo
T10634 507-508 . denotes .
T10635 508-688 sentence denotes Transgenic expression of APPswe/ind and consequent overproduction of Aβ42 cause early-onset amyloid deposition in untreated mice, in which deposits appear as early as 2 mo of age.
T10636 509-519 JJ denotes Transgenic
T10637 520-530 NN denotes expression
T10639 531-533 IN denotes of
T10640 534-540 NN denotes APPswe
T10642 540-541 HYPH denotes /
T10641 541-544 NN denotes ind
T10643 545-548 CC denotes and
T10644 549-559 JJ denotes consequent
T10645 560-574 NN denotes overproduction
T10646 575-577 IN denotes of
T10647 578-582 NN denotes Aβ42
T10638 583-588 VBP denotes cause
T10648 589-594 JJ denotes early
T10650 594-595 HYPH denotes -
T10649 595-600 NN denotes onset
T10652 601-608 NN denotes amyloid
T10651 609-619 NN denotes deposition
T10653 620-622 IN denotes in
T10654 623-632 JJ denotes untreated
T10655 633-637 NNS denotes mice
T10656 637-639 , denotes ,
T10657 639-641 IN denotes in
T10659 642-647 WDT denotes which
T10660 648-656 NNS denotes deposits
T10658 657-663 VBP denotes appear
T10661 664-666 RB denotes as
T10662 667-672 RB denotes early
T10663 673-675 IN denotes as
T10664 676-677 CD denotes 2
T10665 678-680 NN denotes mo
T10666 681-683 IN denotes of
T10667 684-687 NN denotes age
T10668 687-688 . denotes .
T10669 688-837 sentence denotes Amyloid burden worsens significantly with age, and by 9 mo, the hippocampus and cortex of untreated mice are largely filled with aggregated peptide.
T10670 689-696 NN denotes Amyloid
T10671 697-703 NN denotes burden
T10672 704-711 VBZ denotes worsens
T10673 712-725 RB denotes significantly
T10674 726-730 IN denotes with
T10675 731-734 NN denotes age
T10676 734-736 , denotes ,
T10677 736-739 CC denotes and
T10678 740-742 IN denotes by
T10680 743-744 CD denotes 9
T10681 745-747 NN denotes mo
T10682 747-749 , denotes ,
T10683 749-752 DT denotes the
T10684 753-764 NN denotes hippocampus
T10685 765-768 CC denotes and
T10686 769-775 NN denotes cortex
T10687 776-778 IN denotes of
T10688 779-788 JJ denotes untreated
T10689 789-793 NNS denotes mice
T10690 794-797 VBP denotes are
T10691 798-805 RB denotes largely
T10679 806-812 VBN denotes filled
T10692 813-817 IN denotes with
T10693 818-828 VBN denotes aggregated
T10694 829-836 NN denotes peptide
T10695 836-837 . denotes .
T10696 837-950 sentence denotes We find that suppression of transgenic APP by more than 95% abruptly halts the progression of amyloid pathology.
T10697 838-840 PRP denotes We
T10698 841-845 VBP denotes find
T10699 846-850 IN denotes that
T10701 851-862 NN denotes suppression
T10702 863-865 IN denotes of
T10703 866-876 JJ denotes transgenic
T10704 877-880 NN denotes APP
T10705 881-883 IN denotes by
T10706 884-888 JJR denotes more
T10708 889-893 IN denotes than
T10707 894-896 CD denotes 95
T10709 896-897 NN denotes %
T10710 898-906 RB denotes abruptly
T10700 907-912 VBZ denotes halts
T10711 913-916 DT denotes the
T10712 917-928 NN denotes progression
T10713 929-931 IN denotes of
T10714 932-939 NN denotes amyloid
T10715 940-949 NN denotes pathology
T10716 949-950 . denotes .
T10717 950-1143 sentence denotes Importantly, this outcome occurs in animals already harboring considerable amyloid pathology, a situation similar to what might be expected in patients to be treated with secretase inhibitors.
T10718 951-962 RB denotes Importantly
T10720 962-964 , denotes ,
T10721 964-968 DT denotes this
T10722 969-976 NN denotes outcome
T10719 977-983 VBZ denotes occurs
T10723 984-986 IN denotes in
T10724 987-994 NNS denotes animals
T10725 995-1002 RB denotes already
T10726 1003-1012 VBG denotes harboring
T10727 1013-1025 JJ denotes considerable
T10729 1026-1033 NN denotes amyloid
T10728 1034-1043 NN denotes pathology
T10730 1043-1045 , denotes ,
T10731 1045-1046 DT denotes a
T10732 1047-1056 NN denotes situation
T10733 1057-1064 JJ denotes similar
T10734 1065-1067 IN denotes to
T10735 1068-1072 WP denotes what
T10737 1073-1078 MD denotes might
T10738 1079-1081 VB denotes be
T10736 1082-1090 VBN denotes expected
T10739 1091-1093 IN denotes in
T10740 1094-1102 NNS denotes patients
T10741 1103-1105 TO denotes to
T10743 1106-1108 VB denotes be
T10742 1109-1116 VBN denotes treated
T10744 1117-1121 IN denotes with
T10745 1122-1131 NN denotes secretase
T10746 1132-1142 NNS denotes inhibitors
T10747 1142-1143 . denotes .
T10748 1143-1316 sentence denotes Somewhat unexpectedly, we observe no appreciable clearance of deposited amyloid even following periods of transgene suppression equal to the time taken for plaques to form.
T10749 1144-1152 RB denotes Somewhat
T10750 1153-1165 RB denotes unexpectedly
T10752 1165-1167 , denotes ,
T10753 1167-1169 PRP denotes we
T10751 1170-1177 VBP denotes observe
T10754 1178-1180 DT denotes no
T10756 1181-1192 JJ denotes appreciable
T10755 1193-1202 NN denotes clearance
T10757 1203-1205 IN denotes of
T10758 1206-1215 VBN denotes deposited
T10759 1216-1223 NN denotes amyloid
T10760 1224-1228 RB denotes even
T10761 1229-1238 VBG denotes following
T10762 1239-1246 NNS denotes periods
T10763 1247-1249 IN denotes of
T10764 1250-1259 NN denotes transgene
T10765 1260-1271 NN denotes suppression
T10766 1272-1277 JJ denotes equal
T10767 1278-1280 IN denotes to
T10768 1281-1284 DT denotes the
T10769 1285-1289 NN denotes time
T10770 1290-1295 VBN denotes taken
T10771 1296-1299 IN denotes for
T10773 1300-1307 NNS denotes plaques
T10774 1308-1310 TO denotes to
T10772 1311-1315 VB denotes form
T10775 1315-1316 . denotes .
T10776 1316-1534 sentence denotes This latter finding indicates that compared to other disease-associated protein aggregates such as mutant huntingtin, which clear in less than 3 mo [32], the disaggregation of extracellular amyloid is relatively slow.
T10777 1317-1321 DT denotes This
T10779 1322-1328 JJ denotes latter
T10778 1329-1336 NN denotes finding
T10780 1337-1346 VBZ denotes indicates
T10781 1347-1351 IN denotes that
T10783 1352-1360 VBN denotes compared
T10784 1361-1363 IN denotes to
T10785 1364-1369 JJ denotes other
T10787 1370-1377 NN denotes disease
T10789 1377-1378 HYPH denotes -
T10788 1378-1388 VBN denotes associated
T10790 1389-1396 NN denotes protein
T10786 1397-1407 NNS denotes aggregates
T10791 1408-1412 JJ denotes such
T10792 1413-1415 IN denotes as
T10793 1416-1422 NN denotes mutant
T10794 1423-1433 NN denotes huntingtin
T10795 1433-1435 , denotes ,
T10796 1435-1440 WDT denotes which
T10797 1441-1446 VBP denotes clear
T10798 1447-1449 IN denotes in
T10799 1450-1454 JJR denotes less
T10801 1455-1459 IN denotes than
T10800 1460-1461 CD denotes 3
T10802 1462-1464 NN denotes mo
T10803 1465-1466 -LRB- denotes [
T10804 1466-1468 CD denotes 32
T10805 1468-1469 -RRB- denotes ]
T10806 1469-1471 , denotes ,
T10807 1471-1474 DT denotes the
T10808 1475-1489 NN denotes disaggregation
T10809 1490-1492 IN denotes of
T10810 1493-1506 JJ denotes extracellular
T10811 1507-1514 NN denotes amyloid
T10782 1515-1517 VBZ denotes is
T10812 1518-1528 RB denotes relatively
T10813 1529-1533 JJ denotes slow
T10814 1533-1534 . denotes .
T10815 1534-1705 sentence denotes Notably, pharmaceutical γ-secretase inhibitors published to date show less strict regulation of Aβ production following chronic administration than we have attained here.
T10816 1535-1542 RB denotes Notably
T10818 1542-1544 , denotes ,
T10819 1544-1558 JJ denotes pharmaceutical
T10821 1559-1560 SYM denotes γ
T10823 1560-1561 HYPH denotes -
T10822 1561-1570 NN denotes secretase
T10820 1571-1581 NNS denotes inhibitors
T10824 1582-1591 VBN denotes published
T10825 1592-1594 IN denotes to
T10826 1595-1599 NN denotes date
T10817 1600-1604 VBP denotes show
T10827 1605-1609 RBR denotes less
T10828 1610-1616 JJ denotes strict
T10829 1617-1627 NN denotes regulation
T10830 1628-1630 IN denotes of
T10831 1631-1633 NN denotes Aβ
T10832 1634-1644 NN denotes production
T10833 1645-1654 VBG denotes following
T10834 1655-1662 JJ denotes chronic
T10835 1663-1677 NN denotes administration
T10836 1678-1682 IN denotes than
T10838 1683-1685 PRP denotes we
T10839 1686-1690 VBP denotes have
T10837 1691-1699 VBN denotes attained
T10840 1700-1704 RB denotes here
T10841 1704-1705 . denotes .
T10842 1705-1915 sentence denotes Two independent compounds tested in Tg2576 [33] and TgCRND8 [34] transgenic mice show no more than 85% suppression of Aβ40 levels, and where measured, even less suppression of Aβ42 (approximately 60%) [35,36].
T10843 1706-1709 CD denotes Two
T10845 1710-1721 JJ denotes independent
T10844 1722-1731 NNS denotes compounds
T10847 1732-1738 VBN denotes tested
T10848 1739-1741 IN denotes in
T10849 1742-1748 NN denotes Tg2576
T10851 1749-1750 -LRB- denotes [
T10852 1750-1752 CD denotes 33
T10853 1752-1753 -RRB- denotes ]
T10854 1754-1757 CC denotes and
T10855 1758-1765 NN denotes TgCRND8
T10856 1766-1767 -LRB- denotes [
T10857 1767-1769 CD denotes 34
T10858 1769-1770 -RRB- denotes ]
T10850 1771-1781 JJ denotes transgenic
T10859 1782-1786 NNS denotes mice
T10846 1787-1791 VBP denotes show
T10860 1792-1794 RB denotes no
T10862 1795-1799 JJR denotes more
T10863 1800-1804 IN denotes than
T10861 1805-1807 CD denotes 85
T10864 1807-1808 NN denotes %
T10865 1809-1820 NN denotes suppression
T10866 1821-1823 IN denotes of
T10867 1824-1828 NN denotes Aβ40
T10868 1829-1835 NNS denotes levels
T10869 1835-1837 , denotes ,
T10870 1837-1840 CC denotes and
T10871 1841-1846 WRB denotes where
T10872 1847-1855 VBN denotes measured
T10874 1855-1857 , denotes ,
T10875 1857-1861 RB denotes even
T10876 1862-1866 JJR denotes less
T10873 1867-1878 NN denotes suppression
T10877 1879-1881 IN denotes of
T10878 1882-1886 NN denotes Aβ42
T10879 1887-1888 -LRB- denotes (
T10881 1888-1901 RB denotes approximately
T10882 1902-1904 CD denotes 60
T10880 1904-1905 NN denotes %
T10883 1905-1906 -RRB- denotes )
T10884 1907-1908 -LRB- denotes [
T10886 1908-1910 CD denotes 35
T10887 1910-1911 , denotes ,
T10885 1911-1913 CD denotes 36
T10888 1913-1914 -RRB- denotes ]
T10889 1914-1915 . denotes .
T10890 1915-2187 sentence denotes Thus, even after accounting for the much higher APP expression levels in our mice than in the Tg2576 and TgCRND8 lines, we have achieved better absolute suppression of Aβ production with the tet-off system than is currently possible with published γ-secretase inhibitors.
T10891 1916-1920 RB denotes Thus
T10893 1920-1922 , denotes ,
T10894 1922-1926 RB denotes even
T10895 1927-1932 IN denotes after
T10896 1933-1943 VBG denotes accounting
T10897 1944-1947 IN denotes for
T10898 1948-1951 DT denotes the
T10900 1952-1956 RB denotes much
T10901 1957-1963 JJR denotes higher
T10902 1964-1967 NN denotes APP
T10903 1968-1978 NN denotes expression
T10899 1979-1985 NNS denotes levels
T10904 1986-1988 IN denotes in
T10905 1989-1992 PRP$ denotes our
T10906 1993-1997 NNS denotes mice
T10907 1998-2002 IN denotes than
T10908 2003-2005 IN denotes in
T10909 2006-2009 DT denotes the
T10911 2010-2016 NN denotes Tg2576
T10912 2017-2020 CC denotes and
T10913 2021-2028 NN denotes TgCRND8
T10910 2029-2034 NNS denotes lines
T10914 2034-2036 , denotes ,
T10915 2036-2038 PRP denotes we
T10916 2039-2043 VBP denotes have
T10892 2044-2052 VBN denotes achieved
T10917 2053-2059 RBR denotes better
T10919 2060-2068 JJ denotes absolute
T10918 2069-2080 NN denotes suppression
T10920 2081-2083 IN denotes of
T10921 2084-2086 NN denotes Aβ
T10922 2087-2097 NN denotes production
T10923 2098-2102 IN denotes with
T10924 2103-2106 DT denotes the
T10926 2107-2110 NN denotes tet
T10928 2110-2111 HYPH denotes -
T10927 2111-2114 NN denotes off
T10925 2115-2121 NN denotes system
T10929 2122-2126 IN denotes than
T10930 2127-2129 VBZ denotes is
T10931 2130-2139 RB denotes currently
T10932 2140-2148 JJ denotes possible
T10933 2149-2153 IN denotes with
T10934 2154-2163 VBN denotes published
T10936 2164-2165 SYM denotes γ
T10938 2165-2166 HYPH denotes -
T10937 2166-2175 NN denotes secretase
T10935 2176-2186 NNS denotes inhibitors
T10939 2186-2187 . denotes .
T10940 2187-2419 sentence denotes Since even the most advanced future pharmaceutical agents are unlikely to attain more complete control of Aβ production than achieved here, this system provides a salient test of therapeutic intervention with Aβ-lowering compounds.
T10941 2188-2193 IN denotes Since
T10943 2194-2198 RB denotes even
T10945 2199-2202 DT denotes the
T10946 2203-2207 RBS denotes most
T10947 2208-2216 JJ denotes advanced
T10948 2217-2223 JJ denotes future
T10949 2224-2238 JJ denotes pharmaceutical
T10944 2239-2245 NNS denotes agents
T10942 2246-2249 VBP denotes are
T10951 2250-2258 JJ denotes unlikely
T10952 2259-2261 TO denotes to
T10953 2262-2268 VB denotes attain
T10954 2269-2273 RBR denotes more
T10955 2274-2282 JJ denotes complete
T10956 2283-2290 NN denotes control
T10957 2291-2293 IN denotes of
T10958 2294-2296 NN denotes Aβ
T10959 2297-2307 NN denotes production
T10960 2308-2312 IN denotes than
T10961 2313-2321 VBN denotes achieved
T10962 2322-2326 RB denotes here
T10963 2326-2328 , denotes ,
T10964 2328-2332 DT denotes this
T10965 2333-2339 NN denotes system
T10950 2340-2348 VBZ denotes provides
T10966 2349-2350 DT denotes a
T10968 2351-2358 JJ denotes salient
T10967 2359-2363 NN denotes test
T10969 2364-2366 IN denotes of
T10970 2367-2378 JJ denotes therapeutic
T10971 2379-2391 NN denotes intervention
T10972 2392-2396 IN denotes with
T10973 2397-2399 NN denotes Aβ
T10975 2399-2400 HYPH denotes -
T10974 2400-2408 VBG denotes lowering
T10976 2409-2418 NNS denotes compounds
T10977 2418-2419 . denotes .
T10978 2419-2607 sentence denotes Although the progression of amyloid deposition was sharply arrested by this approach, we found that a substantial amyloid burden remained even after long periods of transgene suppression.
T10979 2420-2428 IN denotes Although
T10981 2429-2432 DT denotes the
T10982 2433-2444 NN denotes progression
T10983 2445-2447 IN denotes of
T10984 2448-2455 NN denotes amyloid
T10985 2456-2466 NN denotes deposition
T10986 2467-2470 VBD denotes was
T10987 2471-2478 RB denotes sharply
T10980 2479-2487 VBN denotes arrested
T10989 2488-2490 IN denotes by
T10990 2491-2495 DT denotes this
T10991 2496-2504 NN denotes approach
T10992 2504-2506 , denotes ,
T10993 2506-2508 PRP denotes we
T10988 2509-2514 VBD denotes found
T10994 2515-2519 IN denotes that
T10996 2520-2521 DT denotes a
T10998 2522-2533 JJ denotes substantial
T10999 2534-2541 NN denotes amyloid
T10997 2542-2548 NN denotes burden
T10995 2549-2557 VBD denotes remained
T11000 2558-2562 RB denotes even
T11001 2563-2568 IN denotes after
T11002 2569-2573 JJ denotes long
T11003 2574-2581 NNS denotes periods
T11004 2582-2584 IN denotes of
T11005 2585-2594 NN denotes transgene
T11006 2595-2606 NN denotes suppression
T11007 2606-2607 . denotes .
T11008 2607-2766 sentence denotes We examined a small number of animals after 12 mo of dox treatment (beginning at 6 mo of age), and found that amyloid deposits were still relatively abundant.
T11009 2608-2610 PRP denotes We
T11010 2611-2619 VBD denotes examined
T11011 2620-2621 DT denotes a
T11013 2622-2627 JJ denotes small
T11012 2628-2634 NN denotes number
T11014 2635-2637 IN denotes of
T11015 2638-2645 NNS denotes animals
T11016 2646-2651 IN denotes after
T11017 2652-2654 CD denotes 12
T11018 2655-2657 NN denotes mo
T11019 2658-2660 IN denotes of
T11020 2661-2664 NN denotes dox
T11021 2665-2674 NN denotes treatment
T11022 2675-2676 -LRB- denotes (
T11023 2676-2685 VBG denotes beginning
T11024 2686-2688 IN denotes at
T11025 2689-2690 CD denotes 6
T11026 2691-2693 NN denotes mo
T11027 2694-2696 IN denotes of
T11028 2697-2700 NN denotes age
T11029 2700-2701 -RRB- denotes )
T11030 2701-2703 , denotes ,
T11031 2703-2706 CC denotes and
T11032 2707-2712 VBD denotes found
T11033 2713-2717 IN denotes that
T11035 2718-2725 NN denotes amyloid
T11036 2726-2734 NNS denotes deposits
T11034 2735-2739 VBD denotes were
T11037 2740-2745 RB denotes still
T11038 2746-2756 RB denotes relatively
T11039 2757-2765 JJ denotes abundant
T11040 2765-2766 . denotes .
T11041 2766-2810 sentence denotes Longer-term treatments are now in progress.
T11042 2767-2773 JJ denotes Longer
T11044 2773-2774 HYPH denotes -
T11043 2774-2778 NN denotes term
T11045 2779-2789 NNS denotes treatments
T11046 2790-2793 VBP denotes are
T11047 2794-2797 RB denotes now
T11048 2798-2800 IN denotes in
T11049 2801-2809 NN denotes progress
T11050 2809-2810 . denotes .
T11051 2810-3113 sentence denotes At the latest treatment interval analyzed by ELISA, animals administered dox for 6 mo showed elevated levels of PBS-soluble Aβ (see Figure 5) that could be interpreted as an indication that the plaques are slowly releasing peptide (or oligomeric Aβ) into the soluble pool and might eventually dissolve.
T11052 2811-2813 IN denotes At
T11054 2814-2817 DT denotes the
T11056 2818-2824 JJS denotes latest
T11057 2825-2834 NN denotes treatment
T11055 2835-2843 NN denotes interval
T11058 2844-2852 VBN denotes analyzed
T11059 2853-2855 IN denotes by
T11060 2856-2861 NN denotes ELISA
T11061 2861-2863 , denotes ,
T11062 2863-2870 NNS denotes animals
T11063 2871-2883 VBN denotes administered
T11064 2884-2887 NN denotes dox
T11065 2888-2891 IN denotes for
T11066 2892-2893 CD denotes 6
T11067 2894-2896 NN denotes mo
T11053 2897-2903 VBD denotes showed
T11068 2904-2912 VBN denotes elevated
T11069 2913-2919 NNS denotes levels
T11070 2920-2922 IN denotes of
T11071 2923-2926 NN denotes PBS
T11073 2926-2927 HYPH denotes -
T11072 2927-2934 JJ denotes soluble
T11074 2935-2937 NN denotes Aβ
T11075 2938-2939 -LRB- denotes (
T11076 2939-2942 VB denotes see
T11077 2943-2949 NN denotes Figure
T11078 2950-2951 CD denotes 5
T11079 2951-2952 -RRB- denotes )
T11080 2953-2957 WDT denotes that
T11082 2958-2963 MD denotes could
T11083 2964-2966 VB denotes be
T11081 2967-2978 VBN denotes interpreted
T11084 2979-2981 IN denotes as
T11085 2982-2984 DT denotes an
T11086 2985-2995 NN denotes indication
T11087 2996-3000 IN denotes that
T11089 3001-3004 DT denotes the
T11090 3005-3012 NNS denotes plaques
T11091 3013-3016 VBP denotes are
T11092 3017-3023 RB denotes slowly
T11088 3024-3033 VBG denotes releasing
T11093 3034-3041 NN denotes peptide
T11094 3042-3043 -LRB- denotes (
T11095 3043-3045 CC denotes or
T11096 3046-3056 JJ denotes oligomeric
T11097 3057-3059 NN denotes Aβ
T11098 3059-3060 -RRB- denotes )
T11099 3061-3065 IN denotes into
T11100 3066-3069 DT denotes the
T11102 3070-3077 JJ denotes soluble
T11101 3078-3082 NN denotes pool
T11103 3083-3086 CC denotes and
T11104 3087-3092 MD denotes might
T11106 3093-3103 RB denotes eventually
T11105 3104-3112 VB denotes dissolve
T11107 3112-3113 . denotes .
T11108 3113-3318 sentence denotes Whether inhibiting Aβ production longer than 6 (or 12) mo may ultimately result in clearance of amyloid is under investigation; unfortunately, the life span of the model eventually limits this experiment.
T11109 3114-3121 IN denotes Whether
T11111 3122-3132 VBG denotes inhibiting
T11112 3133-3135 NN denotes Aβ
T11113 3136-3146 NN denotes production
T11114 3147-3153 RBR denotes longer
T11115 3154-3158 IN denotes than
T11116 3159-3160 CD denotes 6
T11118 3161-3162 -LRB- denotes (
T11119 3162-3164 CC denotes or
T11120 3165-3167 CD denotes 12
T11121 3167-3168 -RRB- denotes )
T11117 3169-3171 NN denotes mo
T11122 3172-3175 MD denotes may
T11123 3176-3186 RB denotes ultimately
T11110 3187-3193 VB denotes result
T11125 3194-3196 IN denotes in
T11126 3197-3206 NN denotes clearance
T11127 3207-3209 IN denotes of
T11128 3210-3217 NN denotes amyloid
T11124 3218-3220 VBZ denotes is
T11130 3221-3226 IN denotes under
T11131 3227-3240 NN denotes investigation
T11132 3240-3241 : denotes ;
T11133 3242-3255 RB denotes unfortunately
T11134 3255-3257 , denotes ,
T11135 3257-3260 DT denotes the
T11137 3261-3265 NN denotes life
T11136 3266-3270 NN denotes span
T11138 3271-3273 IN denotes of
T11139 3274-3277 DT denotes the
T11140 3278-3283 NN denotes model
T11141 3284-3294 RB denotes eventually
T11129 3295-3301 VBZ denotes limits
T11142 3302-3306 DT denotes this
T11143 3307-3317 NN denotes experiment
T11144 3317-3318 . denotes .
T11145 3318-3442 sentence denotes Therapeutics used in humans will have considerably more time to act than is possible within the life span of rodent models.
T11146 3319-3331 NNS denotes Therapeutics
T11148 3332-3336 VBN denotes used
T11149 3337-3339 IN denotes in
T11150 3340-3346 NNS denotes humans
T11151 3347-3351 MD denotes will
T11147 3352-3356 VB denotes have
T11152 3357-3369 RB denotes considerably
T11153 3370-3374 JJR denotes more
T11154 3375-3379 NN denotes time
T11155 3380-3382 TO denotes to
T11156 3383-3386 VB denotes act
T11157 3387-3391 IN denotes than
T11158 3392-3394 VBZ denotes is
T11159 3395-3403 JJ denotes possible
T11160 3404-3410 IN denotes within
T11161 3411-3414 DT denotes the
T11163 3415-3419 NN denotes life
T11162 3420-3424 NN denotes span
T11164 3425-3427 IN denotes of
T11165 3428-3434 NN denotes rodent
T11166 3435-3441 NNS denotes models
T11167 3441-3442 . denotes .
T11168 3442-3532 sentence denotes Long-term treatments would certainly be possible and could be a key to effective therapy.
T11169 3443-3447 JJ denotes Long
T11171 3447-3448 HYPH denotes -
T11170 3448-3452 NN denotes term
T11172 3453-3463 NNS denotes treatments
T11174 3464-3469 MD denotes would
T11175 3470-3479 RB denotes certainly
T11173 3480-3482 VB denotes be
T11176 3483-3491 JJ denotes possible
T11177 3492-3495 CC denotes and
T11178 3496-3501 MD denotes could
T11179 3502-3504 VB denotes be
T11180 3505-3506 DT denotes a
T11181 3507-3510 NN denotes key
T11182 3511-3513 IN denotes to
T11183 3514-3523 JJ denotes effective
T11184 3524-3531 NN denotes therapy
T11185 3531-3532 . denotes .
T11186 3532-3829 sentence denotes Overall, however, we interpret our findings as evidence that AD therapies that significantly lower the production of Aβ (by either inhibiting secretase activity or inhibiting APP expression) may not quickly reverse preexisting pathology, but should effectively halt further deposition of amyloid.
T11187 3533-3540 RB denotes Overall
T11189 3540-3542 , denotes ,
T11190 3542-3549 RB denotes however
T11191 3549-3551 , denotes ,
T11192 3551-3553 PRP denotes we
T11188 3554-3563 VBP denotes interpret
T11193 3564-3567 PRP$ denotes our
T11194 3568-3576 NNS denotes findings
T11195 3577-3579 IN denotes as
T11196 3580-3588 NN denotes evidence
T11197 3589-3593 IN denotes that
T11199 3594-3596 NN denotes AD
T11200 3597-3606 NNS denotes therapies
T11201 3607-3611 WDT denotes that
T11203 3612-3625 RB denotes significantly
T11202 3626-3631 VBP denotes lower
T11204 3632-3635 DT denotes the
T11205 3636-3646 NN denotes production
T11206 3647-3649 IN denotes of
T11207 3650-3652 NN denotes Aβ
T11208 3653-3654 -LRB- denotes (
T11209 3654-3656 IN denotes by
T11210 3657-3663 CC denotes either
T11211 3664-3674 VBG denotes inhibiting
T11212 3675-3684 NN denotes secretase
T11213 3685-3693 NN denotes activity
T11214 3694-3696 CC denotes or
T11215 3697-3707 VBG denotes inhibiting
T11216 3708-3711 NN denotes APP
T11217 3712-3722 NN denotes expression
T11218 3722-3723 -RRB- denotes )
T11219 3724-3727 MD denotes may
T11220 3728-3731 RB denotes not
T11221 3732-3739 RB denotes quickly
T11198 3740-3747 VB denotes reverse
T11222 3748-3759 JJ denotes preexisting
T11223 3760-3769 NN denotes pathology
T11224 3769-3771 , denotes ,
T11225 3771-3774 CC denotes but
T11226 3775-3781 MD denotes should
T11228 3782-3793 RB denotes effectively
T11227 3794-3798 VB denotes halt
T11229 3799-3806 JJ denotes further
T11230 3807-3817 NN denotes deposition
T11231 3818-3820 IN denotes of
T11232 3821-3828 NN denotes amyloid
T11233 3828-3829 . denotes .
T11234 3829-4147 sentence denotes In interpreting our study, it should be remembered that the earliest plaques to appear in these mice, like other APP transgenics harboring the Swedish mutation [27], are predominantly fibrillar deposits, which may be less tractable than the diffuse aggregates thought to come first in the course of the human disease.
T11235 3830-3832 IN denotes In
T11237 3833-3845 VBG denotes interpreting
T11238 3846-3849 PRP$ denotes our
T11239 3850-3855 NN denotes study
T11240 3855-3857 , denotes ,
T11241 3857-3859 PRP denotes it
T11242 3860-3866 MD denotes should
T11243 3867-3869 VB denotes be
T11236 3870-3880 VBN denotes remembered
T11244 3881-3885 IN denotes that
T11246 3886-3889 DT denotes the
T11248 3890-3898 JJS denotes earliest
T11247 3899-3906 NNS denotes plaques
T11249 3907-3909 TO denotes to
T11250 3910-3916 VB denotes appear
T11251 3917-3919 IN denotes in
T11252 3920-3925 DT denotes these
T11253 3926-3930 NNS denotes mice
T11254 3930-3932 , denotes ,
T11255 3932-3936 IN denotes like
T11256 3937-3942 JJ denotes other
T11258 3943-3946 NN denotes APP
T11257 3947-3958 NNS denotes transgenics
T11259 3959-3968 VBG denotes harboring
T11260 3969-3972 DT denotes the
T11262 3973-3980 JJ denotes Swedish
T11261 3981-3989 NN denotes mutation
T11263 3990-3991 -LRB- denotes [
T11264 3991-3993 CD denotes 27
T11265 3993-3994 -RRB- denotes ]
T11266 3994-3996 , denotes ,
T11245 3996-3999 VBP denotes are
T11267 4000-4013 RB denotes predominantly
T11268 4014-4023 JJ denotes fibrillar
T11269 4024-4032 NNS denotes deposits
T11270 4032-4034 , denotes ,
T11271 4034-4039 WDT denotes which
T11273 4040-4043 MD denotes may
T11272 4044-4046 VB denotes be
T11274 4047-4051 RBR denotes less
T11275 4052-4061 JJ denotes tractable
T11276 4062-4066 IN denotes than
T11277 4067-4070 DT denotes the
T11279 4071-4078 JJ denotes diffuse
T11278 4079-4089 NNS denotes aggregates
T11280 4090-4097 VBN denotes thought
T11281 4098-4100 TO denotes to
T11282 4101-4105 VB denotes come
T11283 4106-4111 RB denotes first
T11284 4112-4114 IN denotes in
T11285 4115-4118 DT denotes the
T11286 4119-4125 NN denotes course
T11287 4126-4128 IN denotes of
T11288 4129-4132 DT denotes the
T11290 4133-4138 JJ denotes human
T11289 4139-4146 NN denotes disease
T11291 4146-4147 . denotes .
T11292 4147-4308 sentence denotes However, our data suggest that once diffuse deposits are formed in these mice, they are no more easily cleared in our system than cored plaques (see Figure S4).
T11293 4148-4155 RB denotes However
T11295 4155-4157 , denotes ,
T11296 4157-4160 PRP$ denotes our
T11297 4161-4165 NNS denotes data
T11294 4166-4173 VBP denotes suggest
T11298 4174-4178 IN denotes that
T11300 4179-4183 IN denotes once
T11302 4184-4191 JJ denotes diffuse
T11303 4192-4200 NNS denotes deposits
T11304 4201-4204 VBP denotes are
T11301 4205-4211 VBN denotes formed
T11305 4212-4214 IN denotes in
T11306 4215-4220 DT denotes these
T11307 4221-4225 NNS denotes mice
T11308 4225-4227 , denotes ,
T11309 4227-4231 PRP denotes they
T11310 4232-4235 VBP denotes are
T11311 4236-4238 RB denotes no
T11312 4239-4243 RBR denotes more
T11313 4244-4250 RB denotes easily
T11299 4251-4258 VBN denotes cleared
T11314 4259-4261 IN denotes in
T11315 4262-4265 PRP$ denotes our
T11316 4266-4272 NN denotes system
T11317 4273-4277 IN denotes than
T11318 4278-4283 VBN denotes cored
T11319 4284-4291 NNS denotes plaques
T11320 4292-4293 -LRB- denotes (
T11321 4293-4296 VB denotes see
T11322 4297-4303 NN denotes Figure
T11323 4304-4306 NN denotes S4
T11324 4306-4307 -RRB- denotes )
T11325 4307-4308 . denotes .
T11326 4308-4484 sentence denotes An additional consideration we recognize is that a small amount of transgene expression continues in the presence of dox and that endogenous mouse Aβ continues to be produced.
T11327 4309-4311 DT denotes An
T11329 4312-4322 JJ denotes additional
T11328 4323-4336 NN denotes consideration
T11331 4337-4339 PRP denotes we
T11332 4340-4349 VBP denotes recognize
T11330 4350-4352 VBZ denotes is
T11333 4353-4357 IN denotes that
T11335 4358-4359 DT denotes a
T11337 4360-4365 JJ denotes small
T11336 4366-4372 NN denotes amount
T11338 4373-4375 IN denotes of
T11339 4376-4385 NN denotes transgene
T11340 4386-4396 NN denotes expression
T11334 4397-4406 VBZ denotes continues
T11341 4407-4409 IN denotes in
T11342 4410-4413 DT denotes the
T11343 4414-4422 NN denotes presence
T11344 4423-4425 IN denotes of
T11345 4426-4429 NN denotes dox
T11346 4430-4433 CC denotes and
T11347 4434-4438 IN denotes that
T11349 4439-4449 JJ denotes endogenous
T11351 4450-4455 NN denotes mouse
T11350 4456-4458 NN denotes Aβ
T11348 4459-4468 VBZ denotes continues
T11352 4469-4471 TO denotes to
T11354 4472-4474 VB denotes be
T11353 4475-4483 VBN denotes produced
T11355 4483-4484 . denotes .
T11356 4484-4629 sentence denotes It is possible that the combined low levels of endogenous mouse Aβ and nonsuppressed human peptide are sufficient to maintain existing deposits.
T11357 4485-4487 PRP denotes It
T11358 4488-4490 VBZ denotes is
T11359 4491-4499 JJ denotes possible
T11360 4500-4504 IN denotes that
T11362 4505-4508 DT denotes the
T11364 4509-4517 VBN denotes combined
T11365 4518-4521 JJ denotes low
T11363 4522-4528 NNS denotes levels
T11366 4529-4531 IN denotes of
T11367 4532-4542 JJ denotes endogenous
T11369 4543-4548 NN denotes mouse
T11368 4549-4551 NN denotes Aβ
T11371 4552-4555 CC denotes and
T11372 4556-4569 JJ denotes nonsuppressed
T11373 4570-4575 JJ denotes human
T11370 4576-4583 NN denotes peptide
T11361 4584-4587 VBP denotes are
T11374 4588-4598 JJ denotes sufficient
T11375 4599-4601 TO denotes to
T11376 4602-4610 VB denotes maintain
T11377 4611-4619 VBG denotes existing
T11378 4620-4628 NNS denotes deposits
T11379 4628-4629 . denotes .
T11380 4629-4834 sentence denotes However, these low levels of peptide are not sufficient to induce new amyloid formation, as CaMKIIα-tTA × tetAPPswe/ind mice raised on dox for up to a year do not develop amyloid lesions (data not shown).
T11381 4630-4637 RB denotes However
T11383 4637-4639 , denotes ,
T11384 4639-4644 DT denotes these
T11386 4645-4648 JJ denotes low
T11385 4649-4655 NNS denotes levels
T11387 4656-4658 IN denotes of
T11388 4659-4666 NN denotes peptide
T11382 4667-4670 VBP denotes are
T11389 4671-4674 RB denotes not
T11390 4675-4685 JJ denotes sufficient
T11391 4686-4688 TO denotes to
T11392 4689-4695 VB denotes induce
T11393 4696-4699 JJ denotes new
T11395 4700-4707 NN denotes amyloid
T11394 4708-4717 NN denotes formation
T11396 4717-4719 , denotes ,
T11397 4719-4721 IN denotes as
T11399 4722-4729 NN denotes CaMKIIα
T11401 4729-4730 HYPH denotes -
T11402 4730-4733 NN denotes tTA
T11403 4734-4735 SYM denotes ×
T11404 4736-4745 NN denotes tetAPPswe
T11405 4745-4746 HYPH denotes /
T11400 4746-4749 NN denotes ind
T11406 4750-4754 NNS denotes mice
T11407 4755-4761 VBN denotes raised
T11408 4762-4764 IN denotes on
T11409 4765-4768 NN denotes dox
T11410 4769-4772 IN denotes for
T11411 4773-4775 IN denotes up
T11413 4776-4778 IN denotes to
T11412 4779-4780 DT denotes a
T11414 4781-4785 NN denotes year
T11415 4786-4788 VBP denotes do
T11416 4789-4792 RB denotes not
T11398 4793-4800 VB denotes develop
T11417 4801-4808 NN denotes amyloid
T11418 4809-4816 NNS denotes lesions
T11419 4817-4818 -LRB- denotes (
T11421 4818-4822 NNS denotes data
T11422 4823-4826 RB denotes not
T11420 4827-4832 VBN denotes shown
T11423 4832-4833 -RRB- denotes )
T11424 4833-4834 . denotes .
T11425 4834-5014 sentence denotes It is also clear that in this genetic system, we have raised the production of Aβ to levels not found in humans to accelerate pathology into an experimentally feasible time frame.
T11426 4835-4837 PRP denotes It
T11427 4838-4840 VBZ denotes is
T11428 4841-4845 RB denotes also
T11429 4846-4851 JJ denotes clear
T11430 4852-4856 IN denotes that
T11432 4857-4859 IN denotes in
T11433 4860-4864 DT denotes this
T11435 4865-4872 JJ denotes genetic
T11434 4873-4879 NN denotes system
T11436 4879-4881 , denotes ,
T11437 4881-4883 PRP denotes we
T11438 4884-4888 VBP denotes have
T11431 4889-4895 VBN denotes raised
T11439 4896-4899 DT denotes the
T11440 4900-4910 NN denotes production
T11441 4911-4913 IN denotes of
T11442 4914-4916 NN denotes Aβ
T11443 4917-4919 IN denotes to
T11444 4920-4926 NNS denotes levels
T11445 4927-4930 RB denotes not
T11446 4931-4936 VBN denotes found
T11447 4937-4939 IN denotes in
T11448 4940-4946 NNS denotes humans
T11449 4947-4949 TO denotes to
T11450 4950-4960 VB denotes accelerate
T11451 4961-4970 NN denotes pathology
T11452 4971-4975 IN denotes into
T11453 4976-4978 DT denotes an
T11455 4979-4993 RB denotes experimentally
T11456 4994-5002 JJ denotes feasible
T11457 5003-5007 NN denotes time
T11454 5008-5013 NN denotes frame
T11458 5013-5014 . denotes .
T11459 5014-5273 sentence denotes This system allowed us to create an approximately 20-fold differential between APP/Aβ synthetic rates before and after treatment, yet the in vivo equilibrium between aggregated and disaggregated states of Aβ still favored the maintenance of amyloid deposits.
T11460 5015-5019 DT denotes This
T11461 5020-5026 NN denotes system
T11462 5027-5034 VBD denotes allowed
T11464 5035-5037 PRP denotes us
T11466 5038-5040 TO denotes to
T11465 5041-5047 VB denotes create
T11467 5048-5050 DT denotes an
T11469 5051-5064 RB denotes approximately
T11470 5065-5072 JJ denotes 20-fold
T11468 5073-5085 NN denotes differential
T11471 5086-5093 IN denotes between
T11472 5094-5097 NN denotes APP
T11474 5097-5098 HYPH denotes /
T11473 5098-5100 NN denotes Aβ
T11476 5101-5110 JJ denotes synthetic
T11475 5111-5116 NNS denotes rates
T11477 5117-5123 IN denotes before
T11478 5124-5127 CC denotes and
T11479 5128-5133 IN denotes after
T11480 5134-5143 NN denotes treatment
T11481 5143-5145 , denotes ,
T11482 5145-5148 RB denotes yet
T11483 5149-5152 DT denotes the
T11485 5153-5155 FW denotes in
T11486 5156-5160 FW denotes vivo
T11484 5161-5172 NN denotes equilibrium
T11487 5173-5180 IN denotes between
T11488 5181-5191 VBN denotes aggregated
T11490 5192-5195 CC denotes and
T11491 5196-5209 VBN denotes disaggregated
T11489 5210-5216 NNS denotes states
T11492 5217-5219 IN denotes of
T11493 5220-5222 NN denotes Aβ
T11494 5223-5228 RB denotes still
T11463 5229-5236 VBD denotes favored
T11495 5237-5240 DT denotes the
T11496 5241-5252 NN denotes maintenance
T11497 5253-5255 IN denotes of
T11498 5256-5263 NN denotes amyloid
T11499 5264-5272 NNS denotes deposits
T11500 5272-5273 . denotes .
T11501 5273-5414 sentence denotes In our opinion, it seems unlikely that amyloid deposits in human brain would be inherently any less stable than those formed in mouse brain.
T11502 5274-5276 IN denotes In
T11504 5277-5280 PRP$ denotes our
T11505 5281-5288 NN denotes opinion
T11506 5288-5290 , denotes ,
T11507 5290-5292 PRP denotes it
T11503 5293-5298 VBZ denotes seems
T11508 5299-5307 JJ denotes unlikely
T11509 5308-5312 IN denotes that
T11511 5313-5320 NN denotes amyloid
T11512 5321-5329 NNS denotes deposits
T11513 5330-5332 IN denotes in
T11514 5333-5338 JJ denotes human
T11515 5339-5344 NN denotes brain
T11516 5345-5350 MD denotes would
T11510 5351-5353 VB denotes be
T11517 5354-5364 RB denotes inherently
T11518 5365-5368 DT denotes any
T11520 5369-5373 RBR denotes less
T11519 5374-5380 JJ denotes stable
T11521 5381-5385 IN denotes than
T11522 5386-5391 DT denotes those
T11523 5392-5398 VBN denotes formed
T11524 5399-5401 IN denotes in
T11525 5402-5407 NN denotes mouse
T11526 5408-5413 NN denotes brain
T11527 5413-5414 . denotes .
T11528 5414-5554 sentence denotes However, the human brain may harbor clearance mechanisms not shared by mice that would allow more efficient removal of preexisting amyloid.
T11529 5415-5422 RB denotes However
T11531 5422-5424 , denotes ,
T11532 5424-5427 DT denotes the
T11534 5428-5433 JJ denotes human
T11533 5434-5439 NN denotes brain
T11535 5440-5443 MD denotes may
T11530 5444-5450 VB denotes harbor
T11536 5451-5460 NN denotes clearance
T11537 5461-5471 NNS denotes mechanisms
T11538 5472-5475 RB denotes not
T11539 5476-5482 VBN denotes shared
T11540 5483-5485 IN denotes by
T11541 5486-5490 NNS denotes mice
T11542 5491-5495 WDT denotes that
T11544 5496-5501 MD denotes would
T11543 5502-5507 VB denotes allow
T11545 5508-5512 RBR denotes more
T11546 5513-5522 JJ denotes efficient
T11547 5523-5530 NN denotes removal
T11548 5531-5533 IN denotes of
T11549 5534-5545 VBG denotes preexisting
T11550 5546-5553 NN denotes amyloid
T11551 5553-5554 . denotes .
T11552 5554-5709 sentence denotes One potential mechanism by which amyloid may be more efficiently removed in the human disease than in the mouse models is through microglial phagocytosis.
T11553 5555-5558 CD denotes One
T11555 5559-5568 JJ denotes potential
T11554 5569-5578 NN denotes mechanism
T11557 5579-5581 IN denotes by
T11559 5582-5587 WDT denotes which
T11560 5588-5595 NN denotes amyloid
T11561 5596-5599 MD denotes may
T11562 5600-5602 VB denotes be
T11563 5603-5607 RBR denotes more
T11564 5608-5619 RB denotes efficiently
T11558 5620-5627 VBN denotes removed
T11565 5628-5630 IN denotes in
T11566 5631-5634 DT denotes the
T11568 5635-5640 JJ denotes human
T11567 5641-5648 NN denotes disease
T11569 5649-5653 IN denotes than
T11570 5654-5656 IN denotes in
T11571 5657-5660 DT denotes the
T11573 5661-5666 NN denotes mouse
T11572 5667-5673 NNS denotes models
T11556 5674-5676 VBZ denotes is
T11574 5677-5684 IN denotes through
T11575 5685-5695 JJ denotes microglial
T11576 5696-5708 NN denotes phagocytosis
T11577 5708-5709 . denotes .
T11578 5709-5850 sentence denotes Resident microglia in transgenic mouse models localize to tissue surrounding plaques but show little evidence of amyloid engulfment [37–40].
T11579 5710-5718 JJ denotes Resident
T11580 5719-5728 NNS denotes microglia
T11582 5729-5731 IN denotes in
T11583 5732-5742 JJ denotes transgenic
T11585 5743-5748 NN denotes mouse
T11584 5749-5755 NNS denotes models
T11581 5756-5764 VBP denotes localize
T11586 5765-5767 IN denotes to
T11587 5768-5774 NN denotes tissue
T11588 5775-5786 VBG denotes surrounding
T11589 5787-5794 NNS denotes plaques
T11590 5795-5798 CC denotes but
T11591 5799-5803 VBP denotes show
T11592 5804-5810 JJ denotes little
T11593 5811-5819 NN denotes evidence
T11594 5820-5822 IN denotes of
T11595 5823-5830 NN denotes amyloid
T11596 5831-5841 NN denotes engulfment
T11597 5842-5843 -LRB- denotes [
T11598 5843-5845 CD denotes 37
T11599 5845-5846 SYM denotes –
T11600 5846-5848 CD denotes 40
T11601 5848-5849 -RRB- denotes ]
T11602 5849-5850 . denotes .
T11603 5850-6008 sentence denotes In contrast, microglia surrounding amyloid plaques in human brain show a much higher state of activation with greater expression of complement receptor [40].
T11604 5851-5853 IN denotes In
T11606 5854-5862 NN denotes contrast
T11607 5862-5864 , denotes ,
T11608 5864-5873 NNS denotes microglia
T11609 5874-5885 VBG denotes surrounding
T11610 5886-5893 NN denotes amyloid
T11611 5894-5901 NNS denotes plaques
T11612 5902-5904 IN denotes in
T11613 5905-5910 JJ denotes human
T11614 5911-5916 NN denotes brain
T11605 5917-5921 VBP denotes show
T11615 5922-5923 DT denotes a
T11617 5924-5928 RB denotes much
T11618 5929-5935 JJR denotes higher
T11616 5936-5941 NN denotes state
T11619 5942-5944 IN denotes of
T11620 5945-5955 NN denotes activation
T11621 5956-5960 IN denotes with
T11622 5961-5968 JJR denotes greater
T11623 5969-5979 NN denotes expression
T11624 5980-5982 IN denotes of
T11625 5983-5993 NN denotes complement
T11626 5994-6002 NN denotes receptor
T11627 6003-6004 -LRB- denotes [
T11628 6004-6006 CD denotes 40
T11629 6006-6007 -RRB- denotes ]
T11630 6007-6008 . denotes .
T11631 6008-6121 sentence denotes Thus, the role of microglia in amyloid metabolism is minor in transgenic models compared to the human condition.
T11632 6009-6013 RB denotes Thus
T11634 6013-6015 , denotes ,
T11635 6015-6018 DT denotes the
T11636 6019-6023 NN denotes role
T11637 6024-6026 IN denotes of
T11638 6027-6036 NNS denotes microglia
T11639 6037-6039 IN denotes in
T11640 6040-6047 NN denotes amyloid
T11641 6048-6058 NN denotes metabolism
T11633 6059-6061 VBZ denotes is
T11642 6062-6067 JJ denotes minor
T11643 6068-6070 IN denotes in
T11644 6071-6081 JJ denotes transgenic
T11645 6082-6088 NNS denotes models
T11646 6089-6097 VBN denotes compared
T11647 6098-6100 IN denotes to
T11648 6101-6104 DT denotes the
T11650 6105-6110 JJ denotes human
T11649 6111-6120 NN denotes condition
T11651 6120-6121 . denotes .
T11652 6121-6412 sentence denotes Somewhat paradoxically, several studies further demonstrate that treatment with anti-inflammatory drugs to reduce microglial activation actually lowers amyloid load in APP transgenic mice, suggesting a role for mouse microglia in the formation and maintenance of amyloid aggregates [41–43].
T11653 6122-6130 RB denotes Somewhat
T11654 6131-6144 RB denotes paradoxically
T11656 6144-6146 , denotes ,
T11657 6146-6153 JJ denotes several
T11658 6154-6161 NNS denotes studies
T11659 6162-6169 RB denotes further
T11655 6170-6181 VBP denotes demonstrate
T11660 6182-6186 IN denotes that
T11662 6187-6196 NN denotes treatment
T11663 6197-6201 IN denotes with
T11664 6202-6219 JJ denotes anti-inflammatory
T11665 6220-6225 NNS denotes drugs
T11666 6226-6228 TO denotes to
T11667 6229-6235 VB denotes reduce
T11668 6236-6246 JJ denotes microglial
T11669 6247-6257 NN denotes activation
T11670 6258-6266 RB denotes actually
T11661 6267-6273 VBZ denotes lowers
T11671 6274-6281 NN denotes amyloid
T11672 6282-6286 NN denotes load
T11673 6287-6289 IN denotes in
T11674 6290-6293 NN denotes APP
T11675 6294-6304 JJ denotes transgenic
T11676 6305-6309 NNS denotes mice
T11677 6309-6311 , denotes ,
T11678 6311-6321 VBG denotes suggesting
T11679 6322-6323 DT denotes a
T11680 6324-6328 NN denotes role
T11681 6329-6332 IN denotes for
T11682 6333-6338 NN denotes mouse
T11683 6339-6348 NNS denotes microglia
T11684 6349-6351 IN denotes in
T11685 6352-6355 DT denotes the
T11686 6356-6365 NN denotes formation
T11687 6366-6369 CC denotes and
T11688 6370-6381 NN denotes maintenance
T11689 6382-6384 IN denotes of
T11690 6385-6392 NN denotes amyloid
T11691 6393-6403 NNS denotes aggregates
T11692 6404-6405 -LRB- denotes [
T11693 6405-6407 CD denotes 41
T11694 6407-6408 SYM denotes –
T11695 6408-6410 CD denotes 43
T11696 6410-6411 -RRB- denotes ]
T11697 6411-6412 . denotes .
T11698 6412-6548 sentence denotes However, this outcome may be alternatively explained by direct effects of many anti-inflammatory drugs on γ-secretase cleavage [44–47].
T11699 6413-6420 RB denotes However
T11701 6420-6422 , denotes ,
T11702 6422-6426 DT denotes this
T11703 6427-6434 NN denotes outcome
T11704 6435-6438 MD denotes may
T11705 6439-6441 VB denotes be
T11706 6442-6455 RB denotes alternatively
T11700 6456-6465 VBN denotes explained
T11707 6466-6468 IN denotes by
T11708 6469-6475 JJ denotes direct
T11709 6476-6483 NNS denotes effects
T11710 6484-6486 IN denotes of
T11711 6487-6491 JJ denotes many
T11713 6492-6509 JJ denotes anti-inflammatory
T11712 6510-6515 NNS denotes drugs
T11714 6516-6518 IN denotes on
T11715 6519-6520 SYM denotes γ
T11717 6520-6521 HYPH denotes -
T11716 6521-6530 NN denotes secretase
T11718 6531-6539 NN denotes cleavage
T11719 6540-6541 -LRB- denotes [
T11720 6541-6543 CD denotes 44
T11721 6543-6544 SYM denotes –
T11722 6544-6546 CD denotes 47
T11723 6546-6547 -RRB- denotes ]
T11724 6547-6548 . denotes .
T11725 6548-6839 sentence denotes Nonetheless, the role of microglia in both the human condition and the mouse models is poorly understood, and differences in microglial reactivity between the two could lead to significantly faster amyloid clearance in the brains of patients with AD than we observe in the tet-off APP mice.
T11726 6549-6560 RB denotes Nonetheless
T11728 6560-6562 , denotes ,
T11729 6562-6565 DT denotes the
T11730 6566-6570 NN denotes role
T11731 6571-6573 IN denotes of
T11732 6574-6583 NNS denotes microglia
T11733 6584-6586 IN denotes in
T11734 6587-6591 CC denotes both
T11736 6592-6595 DT denotes the
T11737 6596-6601 JJ denotes human
T11735 6602-6611 NN denotes condition
T11738 6612-6615 CC denotes and
T11739 6616-6619 DT denotes the
T11741 6620-6625 NN denotes mouse
T11740 6626-6632 NNS denotes models
T11727 6633-6635 VBZ denotes is
T11742 6636-6642 RB denotes poorly
T11743 6643-6653 VBN denotes understood
T11744 6653-6655 , denotes ,
T11745 6655-6658 CC denotes and
T11746 6659-6670 NNS denotes differences
T11748 6671-6673 IN denotes in
T11749 6674-6684 JJ denotes microglial
T11750 6685-6695 NN denotes reactivity
T11751 6696-6703 IN denotes between
T11752 6704-6707 DT denotes the
T11753 6708-6711 CD denotes two
T11754 6712-6717 MD denotes could
T11747 6718-6722 VB denotes lead
T11755 6723-6725 IN denotes to
T11756 6726-6739 RB denotes significantly
T11757 6740-6746 JJR denotes faster
T11759 6747-6754 NN denotes amyloid
T11758 6755-6764 NN denotes clearance
T11760 6765-6767 IN denotes in
T11761 6768-6771 DT denotes the
T11762 6772-6778 NNS denotes brains
T11763 6779-6781 IN denotes of
T11764 6782-6790 NNS denotes patients
T11765 6791-6795 IN denotes with
T11766 6796-6798 NN denotes AD
T11767 6799-6803 IN denotes than
T11769 6804-6806 PRP denotes we
T11768 6807-6814 VBP denotes observe
T11770 6815-6817 IN denotes in
T11771 6818-6821 DT denotes the
T11773 6822-6825 NN denotes tet
T11775 6825-6826 HYPH denotes -
T11774 6826-6829 NN denotes off
T11776 6830-6833 NN denotes APP
T11772 6834-6838 NNS denotes mice
T11777 6838-6839 . denotes .
T11778 6839-7038 sentence denotes Given the relatively minor role played by microglia in other mouse models of amyloidosis, we think it unlikely that these cells have influenced the rate of amyloid clearance in the tet-off APP mice.
T11779 6840-6845 VBN denotes Given
T11781 6846-6849 DT denotes the
T11783 6850-6860 RB denotes relatively
T11784 6861-6866 JJ denotes minor
T11782 6867-6871 NN denotes role
T11785 6872-6878 VBN denotes played
T11786 6879-6881 IN denotes by
T11787 6882-6891 NNS denotes microglia
T11788 6892-6894 IN denotes in
T11789 6895-6900 JJ denotes other
T11791 6901-6906 NN denotes mouse
T11790 6907-6913 NNS denotes models
T11792 6914-6916 IN denotes of
T11793 6917-6928 NN denotes amyloidosis
T11794 6928-6930 , denotes ,
T11795 6930-6932 PRP denotes we
T11780 6933-6938 VBP denotes think
T11796 6939-6941 PRP denotes it
T11797 6942-6950 JJ denotes unlikely
T11798 6951-6955 IN denotes that
T11800 6956-6961 DT denotes these
T11801 6962-6967 NNS denotes cells
T11802 6968-6972 VBP denotes have
T11799 6973-6983 VBN denotes influenced
T11803 6984-6987 DT denotes the
T11804 6988-6992 NN denotes rate
T11805 6993-6995 IN denotes of
T11806 6996-7003 NN denotes amyloid
T11807 7004-7013 NN denotes clearance
T11808 7014-7016 IN denotes in
T11809 7017-7020 DT denotes the
T11811 7021-7024 NN denotes tet
T11813 7024-7025 HYPH denotes -
T11812 7025-7028 NN denotes off
T11814 7029-7032 NN denotes APP
T11810 7033-7037 NNS denotes mice
T11815 7037-7038 . denotes .
T11816 7038-7176 sentence denotes Even so, we considered the possibility that chronic dox treatment may have altered the activation state of microglia in our treated mice.
T11817 7039-7043 RB denotes Even
T11818 7044-7046 RB denotes so
T11820 7046-7048 , denotes ,
T11821 7048-7050 PRP denotes we
T11819 7051-7061 VBD denotes considered
T11822 7062-7065 DT denotes the
T11823 7066-7077 NN denotes possibility
T11824 7078-7082 IN denotes that
T11826 7083-7090 JJ denotes chronic
T11828 7091-7094 NN denotes dox
T11827 7095-7104 NN denotes treatment
T11829 7105-7108 MD denotes may
T11830 7109-7113 VB denotes have
T11825 7114-7121 VBN denotes altered
T11831 7122-7125 DT denotes the
T11833 7126-7136 NN denotes activation
T11832 7137-7142 NN denotes state
T11834 7143-7145 IN denotes of
T11835 7146-7155 NNS denotes microglia
T11836 7156-7158 IN denotes in
T11837 7159-7162 PRP$ denotes our
T11839 7163-7170 VBN denotes treated
T11838 7171-7175 NNS denotes mice
T11840 7175-7176 . denotes .
T11841 7176-7299 sentence denotes Dox is structurally similar to minocycline, a reported anti-inflammatory drug and inhibitor of microglial activation [48].
T11842 7177-7180 NN denotes Dox
T11843 7181-7183 VBZ denotes is
T11844 7184-7196 RB denotes structurally
T11845 7197-7204 JJ denotes similar
T11846 7205-7207 IN denotes to
T11847 7208-7219 NN denotes minocycline
T11848 7219-7221 , denotes ,
T11849 7221-7222 DT denotes a
T11851 7223-7231 VBN denotes reported
T11852 7232-7249 JJ denotes anti-inflammatory
T11850 7250-7254 NN denotes drug
T11853 7255-7258 CC denotes and
T11854 7259-7268 NN denotes inhibitor
T11855 7269-7271 IN denotes of
T11856 7272-7282 JJ denotes microglial
T11857 7283-7293 NN denotes activation
T11858 7294-7295 -LRB- denotes [
T11859 7295-7297 CD denotes 48
T11860 7297-7298 -RRB- denotes ]
T11861 7298-7299 . denotes .
T11862 7299-7489 sentence denotes However, if dox does have anti-inflammatory activity, then, based on previous studies with other anti-inflammatories, we would have expected to find less amyloid in the dox-treated animals.
T11863 7300-7307 RB denotes However
T11865 7307-7309 , denotes ,
T11866 7309-7311 IN denotes if
T11868 7312-7315 NN denotes dox
T11869 7316-7320 VBZ denotes does
T11867 7321-7325 VB denotes have
T11870 7326-7343 JJ denotes anti-inflammatory
T11871 7344-7352 NN denotes activity
T11872 7352-7354 , denotes ,
T11873 7354-7358 RB denotes then
T11874 7358-7360 , denotes ,
T11875 7360-7365 VBN denotes based
T11876 7366-7368 IN denotes on
T11877 7369-7377 JJ denotes previous
T11878 7378-7385 NNS denotes studies
T11879 7386-7390 IN denotes with
T11880 7391-7396 JJ denotes other
T11881 7397-7416 NNS denotes anti-inflammatories
T11882 7416-7418 , denotes ,
T11883 7418-7420 PRP denotes we
T11884 7421-7426 MD denotes would
T11885 7427-7431 VB denotes have
T11864 7432-7440 VBN denotes expected
T11886 7441-7443 TO denotes to
T11887 7444-7448 VB denotes find
T11888 7449-7453 RBR denotes less
T11889 7454-7461 NN denotes amyloid
T11890 7462-7464 IN denotes in
T11891 7465-7468 DT denotes the
T11893 7469-7472 NN denotes dox
T11895 7472-7473 HYPH denotes -
T11894 7473-7480 VBN denotes treated
T11892 7481-7488 NNS denotes animals
T11896 7488-7489 . denotes .
T11897 7489-7521 sentence denotes Clearly, that was not the case.
T11898 7490-7497 RB denotes Clearly
T11900 7497-7499 , denotes ,
T11901 7499-7503 DT denotes that
T11899 7504-7507 VBD denotes was
T11902 7508-7511 RB denotes not
T11903 7512-7515 DT denotes the
T11904 7516-7520 NN denotes case
T11905 7520-7521 . denotes .
T11906 7521-7815 sentence denotes While it is possible that dox acts in some other way to slow amyloid clearance, data from multiple studies demonstrate that microglial responses are normally weak in the mouse AD models [37–40], and thus it is doubtful that dox-mediated microglial inhibition affected the outcome of our study.
T11907 7522-7527 IN denotes While
T11909 7528-7530 PRP denotes it
T11908 7531-7533 VBZ denotes is
T11911 7534-7542 JJ denotes possible
T11912 7543-7547 IN denotes that
T11914 7548-7551 NN denotes dox
T11913 7552-7556 VBZ denotes acts
T11915 7557-7559 IN denotes in
T11916 7560-7564 DT denotes some
T11918 7565-7570 JJ denotes other
T11917 7571-7574 NN denotes way
T11919 7575-7577 TO denotes to
T11920 7578-7582 VB denotes slow
T11921 7583-7590 NN denotes amyloid
T11922 7591-7600 NN denotes clearance
T11923 7600-7602 , denotes ,
T11924 7602-7606 NNS denotes data
T11925 7607-7611 IN denotes from
T11926 7612-7620 JJ denotes multiple
T11927 7621-7628 NNS denotes studies
T11910 7629-7640 VBP denotes demonstrate
T11928 7641-7645 IN denotes that
T11930 7646-7656 JJ denotes microglial
T11931 7657-7666 NNS denotes responses
T11929 7667-7670 VBP denotes are
T11932 7671-7679 RB denotes normally
T11933 7680-7684 JJ denotes weak
T11934 7685-7687 IN denotes in
T11935 7688-7691 DT denotes the
T11937 7692-7697 NN denotes mouse
T11938 7698-7700 NN denotes AD
T11936 7701-7707 NNS denotes models
T11939 7708-7709 -LRB- denotes [
T11940 7709-7711 CD denotes 37
T11941 7711-7712 SYM denotes –
T11942 7712-7714 CD denotes 40
T11943 7714-7715 -RRB- denotes ]
T11944 7715-7717 , denotes ,
T11945 7717-7720 CC denotes and
T11946 7721-7725 RB denotes thus
T11948 7726-7728 PRP denotes it
T11947 7729-7731 VBZ denotes is
T11949 7732-7740 JJ denotes doubtful
T11950 7741-7745 IN denotes that
T11952 7746-7749 NN denotes dox
T11954 7749-7750 HYPH denotes -
T11953 7750-7758 VBN denotes mediated
T11956 7759-7769 JJ denotes microglial
T11955 7770-7780 NN denotes inhibition
T11951 7781-7789 VBD denotes affected
T11957 7790-7793 DT denotes the
T11958 7794-7801 NN denotes outcome
T11959 7802-7804 IN denotes of
T11960 7805-7808 PRP$ denotes our
T11961 7809-7814 NN denotes study
T11962 7814-7815 . denotes .
T11963 7815-7997 sentence denotes The persistence and stability of amyloid deposits in our system is unexpected given the speed with which Aβ aggregates are cleared in other mouse models of therapeutic intervention.
T11964 7816-7819 DT denotes The
T11965 7820-7831 NN denotes persistence
T11967 7832-7835 CC denotes and
T11968 7836-7845 NN denotes stability
T11969 7846-7848 IN denotes of
T11970 7849-7856 NN denotes amyloid
T11971 7857-7865 NNS denotes deposits
T11972 7866-7868 IN denotes in
T11973 7869-7872 PRP$ denotes our
T11974 7873-7879 NN denotes system
T11966 7880-7882 VBZ denotes is
T11975 7883-7893 JJ denotes unexpected
T11976 7894-7899 VBN denotes given
T11977 7900-7903 DT denotes the
T11978 7904-7909 NN denotes speed
T11979 7910-7914 IN denotes with
T11981 7915-7920 WDT denotes which
T11982 7921-7923 NN denotes Aβ
T11983 7924-7934 NNS denotes aggregates
T11984 7935-7938 VBP denotes are
T11980 7939-7946 VBN denotes cleared
T11985 7947-7949 IN denotes in
T11986 7950-7955 JJ denotes other
T11988 7956-7961 NN denotes mouse
T11987 7962-7968 NNS denotes models
T11989 7969-7971 IN denotes of
T11990 7972-7983 JJ denotes therapeutic
T11991 7984-7996 NN denotes intervention
T11992 7996-7997 . denotes .
T11993 7997-8141 sentence denotes Anti-Aβ antibodies injected directly into the brain have been shown to eliminate amyloid deposits in as little as 1 wk after treatment [49–51].
T11994 7998-8005 JJ denotes Anti-Aβ
T11995 8006-8016 NNS denotes antibodies
T11997 8017-8025 VBN denotes injected
T11998 8026-8034 RB denotes directly
T11999 8035-8039 IN denotes into
T12000 8040-8043 DT denotes the
T12001 8044-8049 NN denotes brain
T12002 8050-8054 VBP denotes have
T12003 8055-8059 VBN denotes been
T11996 8060-8065 VBN denotes shown
T12004 8066-8068 TO denotes to
T12005 8069-8078 VB denotes eliminate
T12006 8079-8086 NN denotes amyloid
T12007 8087-8095 NNS denotes deposits
T12008 8096-8098 IN denotes in
T12009 8099-8101 RB denotes as
T12011 8102-8108 JJ denotes little
T12012 8109-8111 IN denotes as
T12010 8112-8113 CD denotes 1
T12013 8114-8116 NN denotes wk
T12014 8117-8122 IN denotes after
T12015 8123-8132 NN denotes treatment
T12016 8133-8134 -LRB- denotes [
T12017 8134-8136 CD denotes 49
T12018 8136-8137 SYM denotes –
T12019 8137-8139 CD denotes 51
T12020 8139-8140 -RRB- denotes ]
T12021 8140-8141 . denotes .
T12022 8141-8358 sentence denotes Peripheral antibody injection decreases amyloid load more broadly, and although it does not appear to act as quickly as local injection, can significantly reduce amyloid load within 2 mo of initial treatment [52,53].
T12023 8142-8152 JJ denotes Peripheral
T12025 8153-8161 NN denotes antibody
T12024 8162-8171 NN denotes injection
T12026 8172-8181 VBZ denotes decreases
T12027 8182-8189 NN denotes amyloid
T12028 8190-8194 NN denotes load
T12029 8195-8199 RBR denotes more
T12030 8200-8207 RB denotes broadly
T12031 8207-8209 , denotes ,
T12032 8209-8212 CC denotes and
T12033 8213-8221 IN denotes although
T12035 8222-8224 PRP denotes it
T12036 8225-8229 VBZ denotes does
T12037 8230-8233 RB denotes not
T12034 8234-8240 VB denotes appear
T12039 8241-8243 TO denotes to
T12040 8244-8247 VB denotes act
T12041 8248-8250 RB denotes as
T12042 8251-8258 RB denotes quickly
T12043 8259-8261 IN denotes as
T12044 8262-8267 JJ denotes local
T12045 8268-8277 NN denotes injection
T12046 8277-8279 , denotes ,
T12047 8279-8282 MD denotes can
T12048 8283-8296 RB denotes significantly
T12038 8297-8303 VB denotes reduce
T12049 8304-8311 NN denotes amyloid
T12050 8312-8316 NN denotes load
T12051 8317-8323 IN denotes within
T12052 8324-8325 CD denotes 2
T12053 8326-8328 NN denotes mo
T12054 8329-8331 IN denotes of
T12055 8332-8339 JJ denotes initial
T12056 8340-8349 NN denotes treatment
T12057 8350-8351 -LRB- denotes [
T12059 8351-8353 CD denotes 52
T12060 8353-8354 , denotes ,
T12058 8354-8356 CD denotes 53
T12061 8356-8357 -RRB- denotes ]
T12062 8357-8358 . denotes .
T12063 8358-8527 sentence denotes More recently, an alternative approach has shown that lentiviral transfer of neprilysin can also reduce the number of aggregates in the area of the injection site [54].
T12064 8359-8363 RBR denotes More
T12065 8364-8372 RB denotes recently
T12067 8372-8374 , denotes ,
T12068 8374-8376 DT denotes an
T12070 8377-8388 JJ denotes alternative
T12069 8389-8397 NN denotes approach
T12071 8398-8401 VBZ denotes has
T12066 8402-8407 VBN denotes shown
T12072 8408-8412 IN denotes that
T12074 8413-8423 JJ denotes lentiviral
T12075 8424-8432 NN denotes transfer
T12076 8433-8435 IN denotes of
T12077 8436-8446 NN denotes neprilysin
T12078 8447-8450 MD denotes can
T12079 8451-8455 RB denotes also
T12073 8456-8462 VB denotes reduce
T12080 8463-8466 DT denotes the
T12081 8467-8473 NN denotes number
T12082 8474-8476 IN denotes of
T12083 8477-8487 NNS denotes aggregates
T12084 8488-8490 IN denotes in
T12085 8491-8494 DT denotes the
T12086 8495-8499 NN denotes area
T12087 8500-8502 IN denotes of
T12088 8503-8506 DT denotes the
T12090 8507-8516 NN denotes injection
T12089 8517-8521 NN denotes site
T12091 8522-8523 -LRB- denotes [
T12092 8523-8525 CD denotes 54
T12093 8525-8526 -RRB- denotes ]
T12094 8526-8527 . denotes .
T12095 8527-8737 sentence denotes Careful study of the mechanism behind several of the antibody-mediated therapies has suggested that activated microglia play an important role in the removal of fibrillar plaques after immunization [50,52,55].
T12096 8528-8535 JJ denotes Careful
T12097 8536-8541 NN denotes study
T12099 8542-8544 IN denotes of
T12100 8545-8548 DT denotes the
T12101 8549-8558 NN denotes mechanism
T12102 8559-8565 IN denotes behind
T12103 8566-8573 JJ denotes several
T12104 8574-8576 IN denotes of
T12105 8577-8580 DT denotes the
T12107 8581-8589 NN denotes antibody
T12109 8589-8590 HYPH denotes -
T12108 8590-8598 VBN denotes mediated
T12106 8599-8608 NNS denotes therapies
T12110 8609-8612 VBZ denotes has
T12098 8613-8622 VBN denotes suggested
T12111 8623-8627 IN denotes that
T12113 8628-8637 VBN denotes activated
T12114 8638-8647 NNS denotes microglia
T12112 8648-8652 VBP denotes play
T12115 8653-8655 DT denotes an
T12117 8656-8665 JJ denotes important
T12116 8666-8670 NN denotes role
T12118 8671-8673 IN denotes in
T12119 8674-8677 DT denotes the
T12120 8678-8685 NN denotes removal
T12121 8686-8688 IN denotes of
T12122 8689-8698 JJ denotes fibrillar
T12123 8699-8706 NNS denotes plaques
T12124 8707-8712 IN denotes after
T12125 8713-8725 NN denotes immunization
T12126 8726-8727 -LRB- denotes [
T12128 8727-8729 CD denotes 50
T12129 8729-8730 , denotes ,
T12130 8730-8732 CD denotes 52
T12131 8732-8733 , denotes ,
T12127 8733-8735 CD denotes 55
T12132 8735-8736 -RRB- denotes ]
T12133 8736-8737 . denotes .
T12134 8737-8982 sentence denotes However, it has been noted that deletion of the Fc receptor (the primary receptor for microglial opsinization of antibody–antigen complexes) in APP transgenic mouse models has no impact on the effectiveness of antibody-mediated therapy [56,57].
T12135 8738-8745 RB denotes However
T12137 8745-8747 , denotes ,
T12138 8747-8749 PRP denotes it
T12139 8750-8753 VBZ denotes has
T12140 8754-8758 VBN denotes been
T12136 8759-8764 VBN denotes noted
T12141 8765-8769 IN denotes that
T12143 8770-8778 NN denotes deletion
T12144 8779-8781 IN denotes of
T12145 8782-8785 DT denotes the
T12147 8786-8788 NN denotes Fc
T12146 8789-8797 NN denotes receptor
T12148 8798-8799 -LRB- denotes (
T12149 8799-8802 DT denotes the
T12151 8803-8810 JJ denotes primary
T12150 8811-8819 NN denotes receptor
T12152 8820-8823 IN denotes for
T12153 8824-8834 JJ denotes microglial
T12154 8835-8847 NN denotes opsinization
T12155 8848-8850 IN denotes of
T12156 8851-8859 NN denotes antibody
T12158 8859-8860 HYPH denotes –
T12157 8860-8867 NN denotes antigen
T12159 8868-8877 NNS denotes complexes
T12160 8877-8878 -RRB- denotes )
T12161 8879-8881 IN denotes in
T12162 8882-8885 NN denotes APP
T12163 8886-8896 JJ denotes transgenic
T12165 8897-8902 NN denotes mouse
T12164 8903-8909 NNS denotes models
T12142 8910-8913 VBZ denotes has
T12166 8914-8916 DT denotes no
T12167 8917-8923 NN denotes impact
T12168 8924-8926 IN denotes on
T12169 8927-8930 DT denotes the
T12170 8931-8944 NN denotes effectiveness
T12171 8945-8947 IN denotes of
T12172 8948-8956 NN denotes antibody
T12174 8956-8957 HYPH denotes -
T12173 8957-8965 VBN denotes mediated
T12175 8966-8973 NN denotes therapy
T12176 8974-8975 -LRB- denotes [
T12178 8975-8977 CD denotes 56
T12179 8977-8978 , denotes ,
T12177 8978-8980 CD denotes 57
T12180 8980-8981 -RRB- denotes ]
T12181 8981-8982 . denotes .
T12182 8982-9253 sentence denotes It is, nevertheless, possible that lack of microglia activation is the major difference between the slow clearance described here, where no perturbation of the immune system is expected, and the rapid clearance described in studies involving antibody or viral injection.
T12183 8983-8985 PRP denotes It
T12184 8986-8988 VBZ denotes is
T12185 8988-8990 , denotes ,
T12186 8990-9002 RB denotes nevertheless
T12187 9002-9004 , denotes ,
T12188 9004-9012 JJ denotes possible
T12189 9013-9017 IN denotes that
T12191 9018-9022 NN denotes lack
T12192 9023-9025 IN denotes of
T12193 9026-9035 NNS denotes microglia
T12194 9036-9046 NN denotes activation
T12190 9047-9049 VBZ denotes is
T12195 9050-9053 DT denotes the
T12197 9054-9059 JJ denotes major
T12196 9060-9070 NN denotes difference
T12198 9071-9078 IN denotes between
T12199 9079-9082 DT denotes the
T12201 9083-9087 JJ denotes slow
T12200 9088-9097 NN denotes clearance
T12202 9098-9107 VBN denotes described
T12203 9108-9112 RB denotes here
T12204 9112-9114 , denotes ,
T12205 9114-9119 WRB denotes where
T12207 9120-9122 DT denotes no
T12208 9123-9135 NN denotes perturbation
T12209 9136-9138 IN denotes of
T12210 9139-9142 DT denotes the
T12212 9143-9149 JJ denotes immune
T12211 9150-9156 NN denotes system
T12213 9157-9159 VBZ denotes is
T12206 9160-9168 VBN denotes expected
T12214 9168-9170 , denotes ,
T12215 9170-9173 CC denotes and
T12216 9174-9177 DT denotes the
T12218 9178-9183 JJ denotes rapid
T12217 9184-9193 NN denotes clearance
T12219 9194-9203 VBN denotes described
T12220 9204-9206 IN denotes in
T12221 9207-9214 NNS denotes studies
T12222 9215-9224 VBG denotes involving
T12223 9225-9233 NN denotes antibody
T12225 9234-9236 CC denotes or
T12226 9237-9242 JJ denotes viral
T12224 9243-9252 NN denotes injection
T12227 9252-9253 . denotes .
T12228 9253-9534 sentence denotes In isolation, mild activation of microglia by injection damage or opsinization may not be adequate to induce substantial phagocytosis, but when combined with an Aβ-lowering agent, such as neprilysin or Aβ-targeted antibodies, the two may work in concert to clear peptide deposits.
T12229 9254-9256 IN denotes In
T12231 9257-9266 NN denotes isolation
T12232 9266-9268 , denotes ,
T12233 9268-9272 JJ denotes mild
T12234 9273-9283 NN denotes activation
T12235 9284-9286 IN denotes of
T12236 9287-9296 NNS denotes microglia
T12237 9297-9299 IN denotes by
T12238 9300-9309 NN denotes injection
T12239 9310-9316 NN denotes damage
T12240 9317-9319 CC denotes or
T12241 9320-9332 NN denotes opsinization
T12242 9333-9336 MD denotes may
T12243 9337-9340 RB denotes not
T12230 9341-9343 VB denotes be
T12244 9344-9352 JJ denotes adequate
T12245 9353-9355 TO denotes to
T12246 9356-9362 VB denotes induce
T12247 9363-9374 JJ denotes substantial
T12248 9375-9387 NN denotes phagocytosis
T12249 9387-9389 , denotes ,
T12250 9389-9392 CC denotes but
T12251 9393-9397 WRB denotes when
T12252 9398-9406 VBN denotes combined
T12254 9407-9411 IN denotes with
T12255 9412-9414 DT denotes an
T12257 9415-9417 NN denotes Aβ
T12259 9417-9418 HYPH denotes -
T12258 9418-9426 VBG denotes lowering
T12256 9427-9432 NN denotes agent
T12260 9432-9434 , denotes ,
T12261 9434-9438 JJ denotes such
T12262 9439-9441 IN denotes as
T12263 9442-9452 NN denotes neprilysin
T12265 9453-9455 CC denotes or
T12266 9456-9458 NN denotes Aβ
T12267 9458-9459 HYPH denotes -
T12264 9459-9467 VBN denotes targeted
T12268 9468-9478 NNS denotes antibodies
T12269 9478-9480 , denotes ,
T12270 9480-9483 DT denotes the
T12271 9484-9487 CD denotes two
T12272 9488-9491 MD denotes may
T12253 9492-9496 VB denotes work
T12273 9497-9499 IN denotes in
T12274 9500-9507 NN denotes concert
T12275 9508-9510 TO denotes to
T12276 9511-9516 VB denotes clear
T12277 9517-9524 NN denotes peptide
T12278 9525-9533 NNS denotes deposits
T12279 9533-9534 . denotes .
T12280 9534-9765 sentence denotes Consistent with this hypothesis, strong activation of microglia through transgenic expression of TGFβ [58] or central injection of lipopolysaccharide [59,60] can by itself substantially reduce plaque burden in APP transgenic mice.
T12281 9535-9545 JJ denotes Consistent
T12283 9546-9550 IN denotes with
T12284 9551-9555 DT denotes this
T12285 9556-9566 NN denotes hypothesis
T12286 9566-9568 , denotes ,
T12287 9568-9574 JJ denotes strong
T12288 9575-9585 NN denotes activation
T12289 9586-9588 IN denotes of
T12290 9589-9598 NNS denotes microglia
T12291 9599-9606 IN denotes through
T12292 9607-9617 JJ denotes transgenic
T12293 9618-9628 NN denotes expression
T12294 9629-9631 IN denotes of
T12295 9632-9636 NN denotes TGFβ
T12296 9637-9638 -LRB- denotes [
T12297 9638-9640 CD denotes 58
T12298 9640-9641 -RRB- denotes ]
T12299 9642-9644 CC denotes or
T12300 9645-9652 JJ denotes central
T12301 9653-9662 NN denotes injection
T12302 9663-9665 IN denotes of
T12303 9666-9684 NN denotes lipopolysaccharide
T12304 9685-9686 -LRB- denotes [
T12306 9686-9688 CD denotes 59
T12307 9688-9689 , denotes ,
T12305 9689-9691 CD denotes 60
T12308 9691-9692 -RRB- denotes ]
T12309 9693-9696 MD denotes can
T12310 9697-9699 IN denotes by
T12311 9700-9706 PRP denotes itself
T12312 9707-9720 RB denotes substantially
T12282 9721-9727 VB denotes reduce
T12313 9728-9734 NN denotes plaque
T12314 9735-9741 NN denotes burden
T12315 9742-9744 IN denotes in
T12316 9745-9748 NN denotes APP
T12317 9749-9759 JJ denotes transgenic
T12318 9760-9764 NNS denotes mice
T12319 9764-9765 . denotes .
T12320 9765-10019 sentence denotes But in the case of acute antibody- and/or injury-mediated activation, once the inflammation has passed, and the antibody and bound peptide have been cleared and degraded, the remaining Aβ quickly reaggregates and amyloid pathology is reestablished [49].
T12321 9766-9769 CC denotes But
T12323 9770-9772 IN denotes in
T12324 9773-9776 DT denotes the
T12325 9777-9781 NN denotes case
T12326 9782-9784 IN denotes of
T12327 9785-9790 JJ denotes acute
T12329 9791-9799 NN denotes antibody
T12331 9799-9800 HYPH denotes -
T12332 9801-9804 CC denotes and
T12333 9804-9805 HYPH denotes /
T12334 9805-9807 CC denotes or
T12335 9808-9814 NN denotes injury
T12336 9814-9815 HYPH denotes -
T12330 9815-9823 VBN denotes mediated
T12328 9824-9834 NN denotes activation
T12337 9834-9836 , denotes ,
T12338 9836-9840 IN denotes once
T12340 9841-9844 DT denotes the
T12341 9845-9857 NN denotes inflammation
T12342 9858-9861 VBZ denotes has
T12339 9862-9868 VBN denotes passed
T12343 9868-9870 , denotes ,
T12344 9870-9873 CC denotes and
T12345 9874-9877 DT denotes the
T12346 9878-9886 NN denotes antibody
T12348 9887-9890 CC denotes and
T12349 9891-9896 VBN denotes bound
T12350 9897-9904 NN denotes peptide
T12351 9905-9909 VBP denotes have
T12352 9910-9914 VBN denotes been
T12347 9915-9922 VBN denotes cleared
T12353 9923-9926 CC denotes and
T12354 9927-9935 VBN denotes degraded
T12355 9935-9937 , denotes ,
T12356 9937-9940 DT denotes the
T12358 9941-9950 VBG denotes remaining
T12357 9951-9953 NN denotes Aβ
T12359 9954-9961 RB denotes quickly
T12322 9962-9974 VBZ denotes reaggregates
T12360 9975-9978 CC denotes and
T12361 9979-9986 NN denotes amyloid
T12362 9987-9996 NN denotes pathology
T12364 9997-9999 VBZ denotes is
T12363 10000-10013 VBN denotes reestablished
T12365 10014-10015 -LRB- denotes [
T12366 10015-10017 CD denotes 49
T12367 10017-10018 -RRB- denotes ]
T12368 10018-10019 . denotes .
T12369 10019-10197 sentence denotes This finding reinforces the notion that without continued stimulation, microglia in mouse models do not maintain the same level of sustained activation that may occur in humans.
T12370 10020-10024 DT denotes This
T12371 10025-10032 NN denotes finding
T12372 10033-10043 VBZ denotes reinforces
T12373 10044-10047 DT denotes the
T12374 10048-10054 NN denotes notion
T12375 10055-10059 IN denotes that
T12377 10060-10067 IN denotes without
T12378 10068-10077 VBN denotes continued
T12379 10078-10089 NN denotes stimulation
T12380 10089-10091 , denotes ,
T12381 10091-10100 NNS denotes microglia
T12382 10101-10103 IN denotes in
T12383 10104-10109 NN denotes mouse
T12384 10110-10116 NNS denotes models
T12385 10117-10119 VBP denotes do
T12386 10120-10123 RB denotes not
T12376 10124-10132 VB denotes maintain
T12387 10133-10136 DT denotes the
T12389 10137-10141 JJ denotes same
T12388 10142-10147 NN denotes level
T12390 10148-10150 IN denotes of
T12391 10151-10160 VBN denotes sustained
T12392 10161-10171 NN denotes activation
T12393 10172-10176 WDT denotes that
T12395 10177-10180 MD denotes may
T12394 10181-10186 VB denotes occur
T12396 10187-10189 IN denotes in
T12397 10190-10196 NNS denotes humans
T12398 10196-10197 . denotes .
T12399 10197-10312 sentence denotes SantaCruz et al. recently published a study of mice that express P301L human tau via a similar vector system [61].
T12400 10198-10207 NNP denotes SantaCruz
T12402 10208-10210 FW denotes et
T12403 10211-10214 FW denotes al.
T12404 10215-10223 RB denotes recently
T12401 10224-10233 VBD denotes published
T12405 10234-10235 DT denotes a
T12406 10236-10241 NN denotes study
T12407 10242-10244 IN denotes of
T12408 10245-10249 NNS denotes mice
T12409 10250-10254 WDT denotes that
T12410 10255-10262 VBP denotes express
T12411 10263-10268 NN denotes P301L
T12413 10269-10274 JJ denotes human
T12412 10275-10278 NN denotes tau
T12414 10279-10282 IN denotes via
T12415 10283-10284 DT denotes a
T12417 10285-10292 JJ denotes similar
T12418 10293-10299 NN denotes vector
T12416 10300-10306 NN denotes system
T12419 10307-10308 -LRB- denotes [
T12420 10308-10310 CD denotes 61
T12421 10310-10311 -RRB- denotes ]
T12422 10311-10312 . denotes .
T12423 10312-10480 sentence denotes As in our tet-off APP mice, SantaCruz et al. found that tau neurofibrillary tangles, like amyloid plaques, are not cleared efficiently following transgene suppression.
T12424 10313-10315 IN denotes As
T12426 10316-10318 IN denotes in
T12427 10319-10322 PRP$ denotes our
T12429 10323-10326 NN denotes tet
T12431 10326-10327 HYPH denotes -
T12430 10327-10330 NN denotes off
T12432 10331-10334 NN denotes APP
T12428 10335-10339 NNS denotes mice
T12433 10339-10341 , denotes ,
T12434 10341-10350 NNP denotes SantaCruz
T12435 10351-10353 FW denotes et
T12436 10354-10357 FW denotes al.
T12425 10358-10363 VBD denotes found
T12437 10364-10368 IN denotes that
T12439 10369-10372 NN denotes tau
T12441 10373-10388 JJ denotes neurofibrillary
T12440 10389-10396 NNS denotes tangles
T12442 10396-10398 , denotes ,
T12443 10398-10402 IN denotes like
T12444 10403-10410 NN denotes amyloid
T12445 10411-10418 NNS denotes plaques
T12446 10418-10420 , denotes ,
T12447 10420-10423 VBP denotes are
T12448 10424-10427 RB denotes not
T12438 10428-10435 VBN denotes cleared
T12449 10436-10447 RB denotes efficiently
T12450 10448-10457 VBG denotes following
T12451 10458-10467 NN denotes transgene
T12452 10468-10479 NN denotes suppression
T12453 10479-10480 . denotes .
T12454 10480-10683 sentence denotes The lack of clearance in both models of AD pathology comes as a stark contrast to the rapid removal of protein aggregates found in similar tet-off mouse models of Huntington [32] and prion disease [62].
T12455 10481-10484 DT denotes The
T12456 10485-10489 NN denotes lack
T12458 10490-10492 IN denotes of
T12459 10493-10502 NN denotes clearance
T12460 10503-10505 IN denotes in
T12461 10506-10510 DT denotes both
T12462 10511-10517 NNS denotes models
T12463 10518-10520 IN denotes of
T12464 10521-10523 NN denotes AD
T12465 10524-10533 NN denotes pathology
T12457 10534-10539 VBZ denotes comes
T12466 10540-10542 IN denotes as
T12467 10543-10544 DT denotes a
T12469 10545-10550 JJ denotes stark
T12468 10551-10559 NN denotes contrast
T12470 10560-10562 IN denotes to
T12471 10563-10566 DT denotes the
T12473 10567-10572 JJ denotes rapid
T12472 10573-10580 NN denotes removal
T12474 10581-10583 IN denotes of
T12475 10584-10591 NN denotes protein
T12476 10592-10602 NNS denotes aggregates
T12477 10603-10608 VBN denotes found
T12478 10609-10611 IN denotes in
T12479 10612-10619 JJ denotes similar
T12481 10620-10623 NN denotes tet
T12483 10623-10624 HYPH denotes -
T12482 10624-10627 NN denotes off
T12484 10628-10633 NN denotes mouse
T12480 10634-10640 NNS denotes models
T12485 10641-10643 IN denotes of
T12486 10644-10654 NNP denotes Huntington
T12488 10655-10656 -LRB- denotes [
T12489 10656-10658 CD denotes 32
T12490 10658-10659 -RRB- denotes ]
T12491 10660-10663 CC denotes and
T12492 10664-10669 NN denotes prion
T12487 10670-10677 NN denotes disease
T12493 10678-10679 -LRB- denotes [
T12494 10679-10681 CD denotes 62
T12495 10681-10682 -RRB- denotes ]
T12496 10682-10683 . denotes .
T12497 10683-10845 sentence denotes In these cases, disrupting the input of new monomer to the system via dox-mediated transgene suppression led to relatively rapid clearance of protein aggregates.
T12498 10684-10686 IN denotes In
T12500 10687-10692 DT denotes these
T12501 10693-10698 NNS denotes cases
T12502 10698-10700 , denotes ,
T12503 10700-10710 VBG denotes disrupting
T12504 10711-10714 DT denotes the
T12505 10715-10720 NN denotes input
T12506 10721-10723 IN denotes of
T12507 10724-10727 JJ denotes new
T12508 10728-10735 NN denotes monomer
T12509 10736-10738 IN denotes to
T12510 10739-10742 DT denotes the
T12511 10743-10749 NN denotes system
T12512 10750-10753 IN denotes via
T12513 10754-10757 NN denotes dox
T12515 10757-10758 HYPH denotes -
T12514 10758-10766 VBN denotes mediated
T12517 10767-10776 NN denotes transgene
T12516 10777-10788 NN denotes suppression
T12499 10789-10792 VBD denotes led
T12518 10793-10795 IN denotes to
T12519 10796-10806 RB denotes relatively
T12520 10807-10812 JJ denotes rapid
T12521 10813-10822 NN denotes clearance
T12522 10823-10825 IN denotes of
T12523 10826-10833 NN denotes protein
T12524 10834-10844 NNS denotes aggregates
T12525 10844-10845 . denotes .
T12526 10845-11000 sentence denotes By contrast, our study and that of SantaCruz et al. suggest that protein aggregates in AD may be more tenacious than in other neurodegenerative disorders.
T12527 10846-10848 IN denotes By
T12529 10849-10857 NN denotes contrast
T12530 10857-10859 , denotes ,
T12531 10859-10862 PRP$ denotes our
T12532 10863-10868 NN denotes study
T12533 10869-10872 CC denotes and
T12534 10873-10877 DT denotes that
T12535 10878-10880 IN denotes of
T12536 10881-10890 NNP denotes SantaCruz
T12537 10891-10893 FW denotes et
T12538 10894-10897 FW denotes al.
T12528 10898-10905 VBP denotes suggest
T12539 10906-10910 IN denotes that
T12541 10911-10918 NN denotes protein
T12542 10919-10929 NNS denotes aggregates
T12543 10930-10932 IN denotes in
T12544 10933-10935 NN denotes AD
T12545 10936-10939 MD denotes may
T12540 10940-10942 VB denotes be
T12546 10943-10947 RBR denotes more
T12547 10948-10957 JJ denotes tenacious
T12548 10958-10962 IN denotes than
T12549 10963-10965 IN denotes in
T12550 10966-10971 JJ denotes other
T12552 10972-10989 JJ denotes neurodegenerative
T12551 10990-10999 NNS denotes disorders
T12553 10999-11000 . denotes .
T12554 11000-11168 sentence denotes Perhaps once aggregated, Aβ and tau are either inherently more stable than other protein aggregates or more resistant to intra- and extracellular clearance mechanisms.
T12555 11001-11008 RB denotes Perhaps
T12557 11009-11013 IN denotes once
T12558 11014-11024 VBN denotes aggregated
T12559 11024-11026 , denotes ,
T12560 11026-11028 NN denotes Aβ
T12561 11029-11032 CC denotes and
T12562 11033-11036 NN denotes tau
T12556 11037-11040 VBP denotes are
T12563 11041-11047 RB denotes either
T12565 11048-11058 RB denotes inherently
T12566 11059-11063 RBR denotes more
T12564 11064-11070 JJ denotes stable
T12567 11071-11075 IN denotes than
T12568 11076-11081 JJ denotes other
T12570 11082-11089 NN denotes protein
T12569 11090-11100 NNS denotes aggregates
T12571 11101-11103 CC denotes or
T12572 11104-11108 RBR denotes more
T12573 11109-11118 JJ denotes resistant
T12574 11119-11121 IN denotes to
T12575 11122-11127 AFX denotes intra
T12577 11127-11128 HYPH denotes -
T12578 11129-11132 CC denotes and
T12576 11133-11146 JJ denotes extracellular
T12580 11147-11156 NN denotes clearance
T12579 11157-11167 NNS denotes mechanisms
T12581 11167-11168 . denotes .
T12582 11168-11309 sentence denotes One question we were not able to address in this study is whether abrogating synthesis of new Aβ halts the progression of cognitive decline.
T12583 11169-11172 CD denotes One
T12584 11173-11181 NN denotes question
T12586 11182-11184 PRP denotes we
T12587 11185-11189 VBD denotes were
T12588 11190-11193 RB denotes not
T12589 11194-11198 JJ denotes able
T12590 11199-11201 TO denotes to
T12591 11202-11209 VB denotes address
T12592 11210-11212 IN denotes in
T12593 11213-11217 DT denotes this
T12594 11218-11223 NN denotes study
T12585 11224-11226 VBZ denotes is
T12595 11227-11234 IN denotes whether
T12597 11235-11245 VBG denotes abrogating
T12598 11246-11255 NN denotes synthesis
T12599 11256-11258 IN denotes of
T12600 11259-11262 JJ denotes new
T12601 11263-11265 NN denotes Aβ
T12596 11266-11271 VBZ denotes halts
T12602 11272-11275 DT denotes the
T12603 11276-11287 NN denotes progression
T12604 11288-11290 IN denotes of
T12605 11291-11300 JJ denotes cognitive
T12606 11301-11308 NN denotes decline
T12607 11308-11309 . denotes .
T12608 11309-11466 sentence denotes Studies from the tet-off tau mice suggest that protein clearance may in fact not be required for cognitive improvement following transgene suppression [61].
T12609 11310-11317 NNS denotes Studies
T12611 11318-11322 IN denotes from
T12612 11323-11326 DT denotes the
T12614 11327-11330 NN denotes tet
T12616 11330-11331 HYPH denotes -
T12615 11331-11334 NN denotes off
T12617 11335-11338 NN denotes tau
T12613 11339-11343 NNS denotes mice
T12610 11344-11351 VBP denotes suggest
T12618 11352-11356 IN denotes that
T12620 11357-11364 NN denotes protein
T12621 11365-11374 NN denotes clearance
T12622 11375-11378 MD denotes may
T12623 11379-11381 IN denotes in
T12624 11382-11386 NN denotes fact
T12625 11387-11390 RB denotes not
T12626 11391-11393 VB denotes be
T12619 11394-11402 VBN denotes required
T12627 11403-11406 IN denotes for
T12628 11407-11416 JJ denotes cognitive
T12629 11417-11428 NN denotes improvement
T12630 11429-11438 VBG denotes following
T12631 11439-11448 NN denotes transgene
T12632 11449-11460 NN denotes suppression
T12633 11461-11462 -LRB- denotes [
T12634 11462-11464 CD denotes 61
T12635 11464-11465 -RRB- denotes ]
T12636 11465-11466 . denotes .
T12637 11466-11662 sentence denotes At present, because of unexpected noncognitive behavioral abnormalities, it is not clear whether the tet-off APP mice can be used to address the same question in the context of amyloid pathology.
T12638 11467-11469 IN denotes At
T12640 11470-11477 JJ denotes present
T12641 11477-11479 , denotes ,
T12642 11479-11486 IN denotes because
T12643 11487-11489 IN denotes of
T12644 11490-11500 JJ denotes unexpected
T12646 11501-11513 JJ denotes noncognitive
T12647 11514-11524 JJ denotes behavioral
T12645 11525-11538 NNS denotes abnormalities
T12648 11538-11540 , denotes ,
T12649 11540-11542 PRP denotes it
T12639 11543-11545 VBZ denotes is
T12650 11546-11549 RB denotes not
T12651 11550-11555 JJ denotes clear
T12652 11556-11563 IN denotes whether
T12654 11564-11567 DT denotes the
T12656 11568-11571 NN denotes tet
T12658 11571-11572 HYPH denotes -
T12657 11572-11575 NN denotes off
T12659 11576-11579 NN denotes APP
T12655 11580-11584 NNS denotes mice
T12660 11585-11588 MD denotes can
T12661 11589-11591 VB denotes be
T12653 11592-11596 VBN denotes used
T12662 11597-11599 TO denotes to
T12663 11600-11607 VB denotes address
T12664 11608-11611 DT denotes the
T12666 11612-11616 JJ denotes same
T12665 11617-11625 NN denotes question
T12667 11626-11628 IN denotes in
T12668 11629-11632 DT denotes the
T12669 11633-11640 NN denotes context
T12670 11641-11643 IN denotes of
T12671 11644-11651 NN denotes amyloid
T12672 11652-11661 NN denotes pathology
T12673 11661-11662 . denotes .
T12674 11662-11814 sentence denotes Both lines of tTA/APP mice we studied here display extreme hyperactivity visible as cage circling and quantified by activity monitoring (see Figure 7).
T12675 11663-11667 DT denotes Both
T12676 11668-11673 NNS denotes lines
T12678 11674-11676 IN denotes of
T12679 11677-11680 NN denotes tTA
T12681 11680-11681 HYPH denotes /
T12680 11681-11684 NN denotes APP
T12682 11685-11689 NNS denotes mice
T12683 11690-11692 PRP denotes we
T12684 11693-11700 VBN denotes studied
T12685 11701-11705 RB denotes here
T12677 11706-11713 VBP denotes display
T12686 11714-11721 JJ denotes extreme
T12687 11722-11735 NN denotes hyperactivity
T12688 11736-11743 JJ denotes visible
T12689 11744-11746 IN denotes as
T12690 11747-11751 NN denotes cage
T12691 11752-11760 NN denotes circling
T12692 11761-11764 CC denotes and
T12693 11765-11775 VBN denotes quantified
T12694 11776-11778 IN denotes by
T12695 11779-11787 NN denotes activity
T12696 11788-11798 NN denotes monitoring
T12697 11799-11800 -LRB- denotes (
T12698 11800-11803 VB denotes see
T12699 11804-11810 NN denotes Figure
T12700 11811-11812 CD denotes 7
T12701 11812-11813 -RRB- denotes )
T12702 11813-11814 . denotes .
T12703 11814-11958 sentence denotes Many of the double transgenic mice showed similar circular patterns of swimming near the edge of the tank when tested in the Morris water maze.
T12704 11815-11819 JJ denotes Many
T12706 11820-11822 IN denotes of
T12707 11823-11826 DT denotes the
T12709 11827-11833 JJ denotes double
T12710 11834-11844 JJ denotes transgenic
T12708 11845-11849 NNS denotes mice
T12705 11850-11856 VBD denotes showed
T12711 11857-11864 JJ denotes similar
T12713 11865-11873 JJ denotes circular
T12712 11874-11882 NNS denotes patterns
T12714 11883-11885 IN denotes of
T12715 11886-11894 NN denotes swimming
T12716 11895-11899 IN denotes near
T12717 11900-11903 DT denotes the
T12718 11904-11908 NN denotes edge
T12719 11909-11911 IN denotes of
T12720 11912-11915 DT denotes the
T12721 11916-11920 NN denotes tank
T12722 11921-11925 WRB denotes when
T12723 11926-11932 VBN denotes tested
T12724 11933-11935 IN denotes in
T12725 11936-11939 DT denotes the
T12727 11940-11946 NNP denotes Morris
T12728 11947-11952 NN denotes water
T12726 11953-11957 NN denotes maze
T12729 11957-11958 . denotes .
T12730 11958-12048 sentence denotes Expression of this phenotype makes standard tests of learning and memory uninterpretable.
T12731 11959-11969 NN denotes Expression
T12733 11970-11972 IN denotes of
T12734 11973-11977 DT denotes this
T12735 11978-11987 NN denotes phenotype
T12732 11988-11993 VBZ denotes makes
T12736 11994-12002 JJ denotes standard
T12737 12003-12008 NNS denotes tests
T12739 12009-12011 IN denotes of
T12740 12012-12020 NN denotes learning
T12741 12021-12024 CC denotes and
T12742 12025-12031 NN denotes memory
T12738 12032-12047 JJ denotes uninterpretable
T12743 12047-12048 . denotes .
T12744 12048-12181 sentence denotes Hyperactivity nonspecifically inhibits choice-driven changes in movement, the key element behind all cognitive behavioral paradigms.
T12745 12049-12062 NN denotes Hyperactivity
T12747 12063-12078 RB denotes nonspecifically
T12746 12079-12087 VBZ denotes inhibits
T12748 12088-12094 NN denotes choice
T12750 12094-12095 HYPH denotes -
T12749 12095-12101 VBN denotes driven
T12751 12102-12109 NNS denotes changes
T12752 12110-12112 IN denotes in
T12753 12113-12121 NN denotes movement
T12754 12121-12123 , denotes ,
T12755 12123-12126 DT denotes the
T12757 12127-12130 JJ denotes key
T12756 12131-12138 NN denotes element
T12758 12139-12145 IN denotes behind
T12759 12146-12149 DT denotes all
T12761 12150-12159 JJ denotes cognitive
T12762 12160-12170 JJ denotes behavioral
T12760 12171-12180 NNS denotes paradigms
T12763 12180-12181 . denotes .
T12764 12181-12330 sentence denotes We are currently working to determine whether hyperactivity correlates with expression of the APPswe/ind holoprotein or its proteolytic derivatives.
T12765 12182-12184 PRP denotes We
T12767 12185-12188 VBP denotes are
T12768 12189-12198 RB denotes currently
T12766 12199-12206 VBG denotes working
T12769 12207-12209 TO denotes to
T12770 12210-12219 VB denotes determine
T12771 12220-12227 IN denotes whether
T12773 12228-12241 NN denotes hyperactivity
T12772 12242-12252 VBZ denotes correlates
T12774 12253-12257 IN denotes with
T12775 12258-12268 NN denotes expression
T12776 12269-12271 IN denotes of
T12777 12272-12275 DT denotes the
T12779 12276-12282 NN denotes APPswe
T12781 12282-12283 HYPH denotes /
T12780 12283-12286 NN denotes ind
T12778 12287-12298 NN denotes holoprotein
T12782 12299-12301 CC denotes or
T12783 12302-12305 PRP$ denotes its
T12785 12306-12317 JJ denotes proteolytic
T12784 12318-12329 NNS denotes derivatives
T12786 12329-12330 . denotes .
T12787 12330-12486 sentence denotes Preliminary studies suggest that hyperactivity does not appear quickly when dox-reared mice are shifted to nonmedicated diets (J. L. J., unpublished data).
T12788 12331-12342 JJ denotes Preliminary
T12789 12343-12350 NNS denotes studies
T12790 12351-12358 VBP denotes suggest
T12791 12359-12363 IN denotes that
T12793 12364-12377 NN denotes hyperactivity
T12794 12378-12382 VBZ denotes does
T12795 12383-12386 RB denotes not
T12792 12387-12393 VB denotes appear
T12796 12394-12401 RB denotes quickly
T12797 12402-12406 WRB denotes when
T12799 12407-12410 NN denotes dox
T12801 12410-12411 HYPH denotes -
T12800 12411-12417 VBN denotes reared
T12802 12418-12422 NNS denotes mice
T12803 12423-12426 VBP denotes are
T12798 12427-12434 VBN denotes shifted
T12804 12435-12437 IN denotes to
T12805 12438-12450 JJ denotes nonmedicated
T12806 12451-12456 NNS denotes diets
T12807 12457-12458 -LRB- denotes (
T12809 12458-12460 NNP denotes J.
T12811 12461-12463 NNP denotes L.
T12810 12464-12466 NNP denotes J.
T12812 12466-12468 , denotes ,
T12813 12468-12479 JJ denotes unpublished
T12808 12480-12484 NNS denotes data
T12814 12484-12485 -RRB- denotes )
T12815 12485-12486 . denotes .
T12816 12486-12652 sentence denotes These data may indicate that the neuroactive culprit is not immediately present after transgenic APP synthesis is initiated, but requires additional time to develop.
T12817 12487-12492 DT denotes These
T12818 12493-12497 NNS denotes data
T12820 12498-12501 MD denotes may
T12819 12502-12510 VB denotes indicate
T12821 12511-12515 IN denotes that
T12823 12516-12519 DT denotes the
T12825 12520-12531 JJ denotes neuroactive
T12824 12532-12539 NN denotes culprit
T12822 12540-12542 VBZ denotes is
T12826 12543-12546 RB denotes not
T12827 12547-12558 RB denotes immediately
T12828 12559-12566 JJ denotes present
T12829 12567-12572 IN denotes after
T12831 12573-12583 JJ denotes transgenic
T12833 12584-12587 NN denotes APP
T12832 12588-12597 NN denotes synthesis
T12834 12598-12600 VBZ denotes is
T12830 12601-12610 VBN denotes initiated
T12835 12610-12612 , denotes ,
T12836 12612-12615 CC denotes but
T12837 12616-12624 VBZ denotes requires
T12838 12625-12635 JJ denotes additional
T12839 12636-12640 NN denotes time
T12840 12641-12643 TO denotes to
T12841 12644-12651 VB denotes develop
T12842 12651-12652 . denotes .
T12843 12652-12783 sentence denotes Alternatively, hyperactivity may be caused by neuronal alterations due to transgene expression during early postnatal development.
T12844 12653-12666 RB denotes Alternatively
T12846 12666-12668 , denotes ,
T12847 12668-12681 NN denotes hyperactivity
T12848 12682-12685 MD denotes may
T12849 12686-12688 VB denotes be
T12845 12689-12695 VBN denotes caused
T12850 12696-12698 IN denotes by
T12851 12699-12707 JJ denotes neuronal
T12852 12708-12719 NNS denotes alterations
T12853 12720-12723 IN denotes due
T12854 12724-12726 IN denotes to
T12855 12727-12736 NN denotes transgene
T12856 12737-12747 NN denotes expression
T12857 12748-12754 IN denotes during
T12858 12755-12760 JJ denotes early
T12859 12761-12770 JJ denotes postnatal
T12860 12771-12782 NN denotes development
T12861 12782-12783 . denotes .
T12862 12783-12858 sentence denotes Further experiments are needed to distinguish between these possibilities.
T12863 12784-12791 JJ denotes Further
T12864 12792-12803 NNS denotes experiments
T12866 12804-12807 VBP denotes are
T12865 12808-12814 VBN denotes needed
T12867 12815-12817 TO denotes to
T12868 12818-12829 VB denotes distinguish
T12869 12830-12837 IN denotes between
T12870 12838-12843 DT denotes these
T12871 12844-12857 NNS denotes possibilities
T12872 12857-12858 . denotes .
T12873 12858-13018 sentence denotes In summary, we demonstrate that abrogating Aβ production halts the progression of pathologic changes in a transgenic mouse model of Alzheimer-type amyloidosis.
T12874 12859-12861 IN denotes In
T12876 12862-12869 NN denotes summary
T12877 12869-12871 , denotes ,
T12878 12871-12873 PRP denotes we
T12875 12874-12885 VBP denotes demonstrate
T12879 12886-12890 IN denotes that
T12881 12891-12901 VBG denotes abrogating
T12882 12902-12904 NN denotes Aβ
T12883 12905-12915 NN denotes production
T12880 12916-12921 VBZ denotes halts
T12884 12922-12925 DT denotes the
T12885 12926-12937 NN denotes progression
T12886 12938-12940 IN denotes of
T12887 12941-12951 JJ denotes pathologic
T12888 12952-12959 NNS denotes changes
T12889 12960-12962 IN denotes in
T12890 12963-12964 DT denotes a
T12892 12965-12975 JJ denotes transgenic
T12893 12976-12981 NN denotes mouse
T12891 12982-12987 NN denotes model
T12894 12988-12990 IN denotes of
T12895 12991-13000 NNP denotes Alzheimer
T12897 13000-13001 HYPH denotes -
T12896 13001-13005 NN denotes type
T12898 13006-13017 NN denotes amyloidosis
T12899 13017-13018 . denotes .
T12900 13018-13153 sentence denotes However, despite dramatic reductions in Aβ synthesis, neuritic plaques are stable structures in vivo that do not quickly disaggregate.
T12901 13019-13026 RB denotes However
T12903 13026-13028 , denotes ,
T12904 13028-13035 IN denotes despite
T12905 13036-13044 JJ denotes dramatic
T12906 13045-13055 NNS denotes reductions
T12907 13056-13058 IN denotes in
T12908 13059-13061 NN denotes Aβ
T12909 13062-13071 NN denotes synthesis
T12910 13071-13073 , denotes ,
T12911 13073-13081 JJ denotes neuritic
T12912 13082-13089 NNS denotes plaques
T12902 13090-13093 VBP denotes are
T12913 13094-13100 JJ denotes stable
T12914 13101-13111 NNS denotes structures
T12915 13112-13114 FW denotes in
T12916 13115-13119 FW denotes vivo
T12917 13120-13124 WDT denotes that
T12919 13125-13127 VBP denotes do
T12920 13128-13131 RB denotes not
T12921 13132-13139 RB denotes quickly
T12918 13140-13152 VB denotes disaggregate
T12922 13152-13153 . denotes .
T12923 13153-13349 sentence denotes It is possible that a combination of therapies to limit Aβ production, increase Aβ degradation, and enhance phagocytosis of deposited amyloid may be required to reverse damage associated with AD.
T12924 13154-13156 PRP denotes It
T12925 13157-13159 VBZ denotes is
T12926 13160-13168 JJ denotes possible
T12927 13169-13173 IN denotes that
T12929 13174-13175 DT denotes a
T12930 13176-13187 NN denotes combination
T12931 13188-13190 IN denotes of
T12932 13191-13200 NNS denotes therapies
T12933 13201-13203 TO denotes to
T12934 13204-13209 VB denotes limit
T12935 13210-13212 NN denotes Aβ
T12936 13213-13223 NN denotes production
T12937 13223-13225 , denotes ,
T12938 13225-13233 VB denotes increase
T12939 13234-13236 NN denotes Aβ
T12940 13237-13248 NN denotes degradation
T12941 13248-13250 , denotes ,
T12942 13250-13253 CC denotes and
T12943 13254-13261 VBP denotes enhance
T12944 13262-13274 NN denotes phagocytosis
T12945 13275-13277 IN denotes of
T12946 13278-13287 VBN denotes deposited
T12947 13288-13295 NN denotes amyloid
T12948 13296-13299 MD denotes may
T12949 13300-13302 VB denotes be
T12928 13303-13311 VBN denotes required
T12950 13312-13314 TO denotes to
T12951 13315-13322 VB denotes reverse
T12952 13323-13329 NN denotes damage
T12953 13330-13340 VBN denotes associated
T12954 13341-13345 IN denotes with
T12955 13346-13348 NN denotes AD
T12956 13348-13349 . denotes .
T12957 13349-13531 sentence denotes However, if started early enough in the course of disease, secretase inhibitors alone could provide substantial benefit in slowing pathogenic processes linked to amyloid deposition.
T12958 13350-13357 RB denotes However
T12960 13357-13359 , denotes ,
T12961 13359-13361 IN denotes if
T12962 13362-13369 VBN denotes started
T12963 13370-13375 RB denotes early
T12964 13376-13382 RB denotes enough
T12965 13383-13385 IN denotes in
T12966 13386-13389 DT denotes the
T12967 13390-13396 NN denotes course
T12968 13397-13399 IN denotes of
T12969 13400-13407 NN denotes disease
T12970 13407-13409 , denotes ,
T12971 13409-13418 NN denotes secretase
T12972 13419-13429 NNS denotes inhibitors
T12973 13430-13435 RB denotes alone
T12974 13436-13441 MD denotes could
T12959 13442-13449 VB denotes provide
T12975 13450-13461 JJ denotes substantial
T12976 13462-13469 NN denotes benefit
T12977 13470-13472 IN denotes in
T12978 13473-13480 VBG denotes slowing
T12979 13481-13491 JJ denotes pathogenic
T12980 13492-13501 NNS denotes processes
T12981 13502-13508 VBN denotes linked
T12982 13509-13511 IN denotes to
T12983 13512-13519 NN denotes amyloid
T12984 13520-13530 NN denotes deposition
T12985 13530-13531 . denotes .
T12986 13531-13766 sentence denotes Even at later stages in the disease, the presence of substantial microglial activation in human AD [40] suggests that simply slowing the formation of new amyloid deposits may allow ongoing phagocytosis to diminish preexisting lesions.
T12987 13532-13536 RB denotes Even
T12988 13537-13539 IN denotes at
T12990 13540-13545 JJR denotes later
T12991 13546-13552 NNS denotes stages
T12992 13553-13555 IN denotes in
T12993 13556-13559 DT denotes the
T12994 13560-13567 NN denotes disease
T12995 13567-13569 , denotes ,
T12996 13569-13572 DT denotes the
T12997 13573-13581 NN denotes presence
T12998 13582-13584 IN denotes of
T12999 13585-13596 JJ denotes substantial
T13001 13597-13607 JJ denotes microglial
T13000 13608-13618 NN denotes activation
T13002 13619-13621 IN denotes in
T13003 13622-13627 JJ denotes human
T13004 13628-13630 NN denotes AD
T13005 13631-13632 -LRB- denotes [
T13006 13632-13634 CD denotes 40
T13007 13634-13635 -RRB- denotes ]
T12989 13636-13644 VBZ denotes suggests
T13008 13645-13649 IN denotes that
T13010 13650-13656 RB denotes simply
T13011 13657-13664 VBG denotes slowing
T13012 13665-13668 DT denotes the
T13013 13669-13678 NN denotes formation
T13014 13679-13681 IN denotes of
T13015 13682-13685 JJ denotes new
T13017 13686-13693 NN denotes amyloid
T13016 13694-13702 NNS denotes deposits
T13018 13703-13706 MD denotes may
T13009 13707-13712 VB denotes allow
T13019 13713-13720 JJ denotes ongoing
T13020 13721-13733 NN denotes phagocytosis
T13022 13734-13736 TO denotes to
T13021 13737-13745 VB denotes diminish
T13023 13746-13757 JJ denotes preexisting
T13024 13758-13765 NNS denotes lesions
T13025 13765-13766 . denotes .
T13026 13766-14005 sentence denotes However, the development of safe and effective secretase inhibitors will ultimately be required to determine whether the human brain has the capacity to repair amyloid-associated damage of AD once the progression of pathology is arrested.
T13027 13767-13774 RB denotes However
T13029 13774-13776 , denotes ,
T13030 13776-13779 DT denotes the
T13031 13780-13791 NN denotes development
T13032 13792-13794 IN denotes of
T13033 13795-13799 JJ denotes safe
T13035 13800-13803 CC denotes and
T13036 13804-13813 JJ denotes effective
T13037 13814-13823 NN denotes secretase
T13034 13824-13834 NNS denotes inhibitors
T13038 13835-13839 MD denotes will
T13039 13840-13850 RB denotes ultimately
T13040 13851-13853 VB denotes be
T13028 13854-13862 VBN denotes required
T13041 13863-13865 TO denotes to
T13042 13866-13875 VB denotes determine
T13043 13876-13883 IN denotes whether
T13045 13884-13887 DT denotes the
T13047 13888-13893 JJ denotes human
T13046 13894-13899 NN denotes brain
T13044 13900-13903 VBZ denotes has
T13048 13904-13907 DT denotes the
T13049 13908-13916 NN denotes capacity
T13050 13917-13919 TO denotes to
T13051 13920-13926 VB denotes repair
T13052 13927-13934 NN denotes amyloid
T13054 13934-13935 HYPH denotes -
T13053 13935-13945 VBN denotes associated
T13055 13946-13952 NN denotes damage
T13056 13953-13955 IN denotes of
T13057 13956-13958 NN denotes AD
T13058 13959-13963 IN denotes once
T13060 13964-13967 DT denotes the
T13061 13968-13979 NN denotes progression
T13062 13980-13982 IN denotes of
T13063 13983-13992 NN denotes pathology
T13064 13993-13995 VBZ denotes is
T13059 13996-14004 VBN denotes arrested
T13065 14004-14005 . denotes .
R6986 T10541 T10542 nsubj We,present
R6987 T10543 T10544 det a,model
R6988 T10544 T10542 dobj model,present
R6989 T10545 T10544 amod new,model
R6990 T10546 T10544 compound mouse,model
R6991 T10547 T10544 prep for,model
R6992 T10548 T10547 pobj AD,for
R6993 T10549 T10550 dep that,designed
R6994 T10550 T10544 relcl designed,model
R6995 T10551 T10550 auxpass was,designed
R6996 T10552 T10553 aux to,test
R6997 T10553 T10550 advcl test,designed
R6998 T10554 T10555 det the,consequences
R6999 T10555 T10553 dobj consequences,test
R7000 T10556 T10555 prep of,consequences
R7001 T10557 T10556 pcomp inhibiting,of
R7002 T10558 T10559 compound Aβ,production
R7003 T10559 T10557 dobj production,inhibiting
R7004 T10560 T10557 prep after,inhibiting
R7005 T10561 T10562 det the,onset
R7006 T10562 T10560 pobj onset,after
R7007 T10563 T10562 prep of,onset
R7008 T10564 T10565 compound amyloid,pathology
R7009 T10565 T10563 pobj pathology,of
R7010 T10566 T10542 punct .,present
R7011 T10568 T10569 amod New,lines
R7012 T10569 T10570 nsubjpass lines,developed
R7013 T10571 T10569 prep of,lines
R7014 T10572 T10573 amod transgenic,mice
R7015 T10573 T10571 pobj mice,of
R7016 T10574 T10570 auxpass were,developed
R7017 T10575 T10570 prep for,developed
R7018 T10576 T10577 det this,study
R7019 T10577 T10575 pobj study,for
R7020 T10578 T10579 dep that,express
R7021 T10579 T10570 ccomp express,developed
R7022 T10580 T10581 amod high,levels
R7023 T10581 T10579 dobj levels,express
R7024 T10582 T10581 prep of,levels
R7025 T10583 T10584 compound APPswe,ind
R7026 T10584 T10582 pobj ind,of
R7027 T10585 T10584 punct /,ind
R7028 T10586 T10579 prep under,express
R7029 T10587 T10588 det the,control
R7030 T10588 T10586 pobj control,under
R7031 T10589 T10588 prep of,control
R7032 T10590 T10591 det a,promoter
R7033 T10591 T10589 pobj promoter,of
R7034 T10592 T10593 npadvmod tetracycline,responsive
R7035 T10593 T10591 amod responsive,promoter
R7036 T10594 T10593 punct -,responsive
R7037 T10595 T10570 punct .,developed
R7038 T10597 T10598 nsubj We,demonstrate
R7039 T10599 T10600 mark that,suppresses
R7040 T10600 T10598 ccomp suppresses,demonstrate
R7041 T10601 T10600 nsubj treatment,suppresses
R7042 T10602 T10601 prep with,treatment
R7043 T10603 T10602 pobj dox,with
R7044 T10604 T10605 amod steady,state
R7045 T10605 T10607 compound state,levels
R7046 T10606 T10605 punct -,state
R7047 T10607 T10600 dobj levels,suppresses
R7048 T10608 T10607 prep of,levels
R7049 T10609 T10610 preconj both,ind
R7050 T10610 T10608 pobj ind,of
R7051 T10611 T10610 compound APPswe,ind
R7052 T10612 T10610 punct /,ind
R7053 T10613 T10610 cc and,ind
R7054 T10614 T10615 poss its,fragments
R7055 T10615 T10610 conj fragments,ind
R7056 T10616 T10615 nmod C,fragments
R7057 T10617 T10615 punct -,fragments
R7058 T10618 T10615 amod terminal,fragments
R7059 T10619 T10600 punct ", ",suppresses
R7060 T10620 T10600 advcl indicating,suppresses
R7061 T10621 T10622 mark that,have
R7062 T10622 T10620 ccomp have,indicating
R7063 T10623 T10624 det the,proteins
R7064 T10624 T10622 nsubj proteins,have
R7065 T10625 T10624 compound mutant,proteins
R7066 T10626 T10627 det a,life
R7067 T10627 T10622 dobj life,have
R7068 T10628 T10629 advmod relatively,short
R7069 T10629 T10627 amod short,life
R7070 T10630 T10627 compound half,life
R7071 T10631 T10627 punct -,life
R7072 T10632 T10633 advmod in,vivo
R7073 T10633 T10622 advmod vivo,have
R7074 T10634 T10598 punct .,demonstrate
R7075 T10636 T10637 amod Transgenic,expression
R7076 T10637 T10638 nsubj expression,cause
R7077 T10639 T10637 prep of,expression
R7078 T10640 T10641 compound APPswe,ind
R7079 T10641 T10639 pobj ind,of
R7080 T10642 T10641 punct /,ind
R7081 T10643 T10637 cc and,expression
R7082 T10644 T10645 amod consequent,overproduction
R7083 T10645 T10637 conj overproduction,expression
R7084 T10646 T10645 prep of,overproduction
R7085 T10647 T10646 pobj Aβ42,of
R7086 T10648 T10649 amod early,onset
R7087 T10649 T10651 compound onset,deposition
R7088 T10650 T10649 punct -,onset
R7089 T10651 T10638 dobj deposition,cause
R7090 T10652 T10651 compound amyloid,deposition
R7091 T10653 T10638 prep in,cause
R7092 T10654 T10655 amod untreated,mice
R7093 T10655 T10653 pobj mice,in
R7094 T10656 T10655 punct ", ",mice
R7095 T10657 T10658 prep in,appear
R7096 T10658 T10655 relcl appear,mice
R7097 T10659 T10657 pobj which,in
R7098 T10660 T10658 nsubj deposits,appear
R7099 T10661 T10662 advmod as,early
R7100 T10662 T10658 advmod early,appear
R7101 T10663 T10662 prep as,early
R7102 T10664 T10665 nummod 2,mo
R7103 T10665 T10663 pobj mo,as
R7104 T10666 T10665 prep of,mo
R7105 T10667 T10666 pobj age,of
R7106 T10668 T10638 punct .,cause
R7107 T10670 T10671 compound Amyloid,burden
R7108 T10671 T10672 nsubj burden,worsens
R7109 T10673 T10672 advmod significantly,worsens
R7110 T10674 T10672 prep with,worsens
R7111 T10675 T10674 pobj age,with
R7112 T10676 T10672 punct ", ",worsens
R7113 T10677 T10672 cc and,worsens
R7114 T10678 T10679 prep by,filled
R7115 T10679 T10672 conj filled,worsens
R7116 T10680 T10681 nummod 9,mo
R7117 T10681 T10678 pobj mo,by
R7118 T10682 T10679 punct ", ",filled
R7119 T10683 T10684 det the,hippocampus
R7120 T10684 T10679 nsubjpass hippocampus,filled
R7121 T10685 T10684 cc and,hippocampus
R7122 T10686 T10684 conj cortex,hippocampus
R7123 T10687 T10684 prep of,hippocampus
R7124 T10688 T10689 amod untreated,mice
R7125 T10689 T10687 pobj mice,of
R7126 T10690 T10679 auxpass are,filled
R7127 T10691 T10679 advmod largely,filled
R7128 T10692 T10679 prep with,filled
R7129 T10693 T10694 amod aggregated,peptide
R7130 T10694 T10692 pobj peptide,with
R7131 T10695 T10679 punct .,filled
R7132 T10697 T10698 nsubj We,find
R7133 T10699 T10700 mark that,halts
R7134 T10700 T10698 ccomp halts,find
R7135 T10701 T10700 nsubj suppression,halts
R7136 T10702 T10701 prep of,suppression
R7137 T10703 T10704 amod transgenic,APP
R7138 T10704 T10702 pobj APP,of
R7139 T10705 T10701 prep by,suppression
R7140 T10706 T10707 amod more,95
R7141 T10707 T10709 nummod 95,%
R7142 T10708 T10707 quantmod than,95
R7143 T10709 T10705 pobj %,by
R7144 T10710 T10700 advmod abruptly,halts
R7145 T10711 T10712 det the,progression
R7146 T10712 T10700 dobj progression,halts
R7147 T10713 T10712 prep of,progression
R7148 T10714 T10715 compound amyloid,pathology
R7149 T10715 T10713 pobj pathology,of
R7150 T10716 T10698 punct .,find
R7151 T10718 T10719 advmod Importantly,occurs
R7152 T10720 T10719 punct ", ",occurs
R7153 T10721 T10722 det this,outcome
R7154 T10722 T10719 nsubj outcome,occurs
R7155 T10723 T10719 prep in,occurs
R7156 T10724 T10723 pobj animals,in
R7157 T10725 T10726 advmod already,harboring
R7158 T10726 T10724 acl harboring,animals
R7159 T10727 T10728 amod considerable,pathology
R7160 T10728 T10726 dobj pathology,harboring
R7161 T10729 T10728 compound amyloid,pathology
R7162 T10730 T10719 punct ", ",occurs
R7163 T10731 T10732 det a,situation
R7164 T10732 T10719 npadvmod situation,occurs
R7165 T10733 T10732 amod similar,situation
R7166 T10734 T10733 prep to,similar
R7167 T10735 T10736 dep what,expected
R7168 T10736 T10734 pcomp expected,to
R7169 T10737 T10736 aux might,expected
R7170 T10738 T10736 auxpass be,expected
R7171 T10739 T10736 prep in,expected
R7172 T10740 T10739 pobj patients,in
R7173 T10741 T10742 aux to,treated
R7174 T10742 T10740 advcl treated,patients
R7175 T10743 T10742 auxpass be,treated
R7176 T10744 T10742 prep with,treated
R7177 T10745 T10746 compound secretase,inhibitors
R7178 T10746 T10744 pobj inhibitors,with
R7179 T10747 T10719 punct .,occurs
R7180 T10749 T10750 advmod Somewhat,unexpectedly
R7181 T10750 T10751 advmod unexpectedly,observe
R7182 T10752 T10751 punct ", ",observe
R7183 T10753 T10751 nsubj we,observe
R7184 T10754 T10755 det no,clearance
R7185 T10755 T10751 dobj clearance,observe
R7186 T10756 T10755 amod appreciable,clearance
R7187 T10757 T10755 prep of,clearance
R7188 T10758 T10759 amod deposited,amyloid
R7189 T10759 T10757 pobj amyloid,of
R7190 T10760 T10761 advmod even,following
R7191 T10761 T10751 prep following,observe
R7192 T10762 T10761 pobj periods,following
R7193 T10763 T10762 prep of,periods
R7194 T10764 T10765 compound transgene,suppression
R7195 T10765 T10763 pobj suppression,of
R7196 T10766 T10762 amod equal,periods
R7197 T10767 T10766 prep to,equal
R7198 T10768 T10769 det the,time
R7199 T10769 T10767 pobj time,to
R7200 T10770 T10769 advcl taken,time
R7201 T10771 T10772 mark for,form
R7202 T10772 T10770 advcl form,taken
R7203 T10773 T10772 nsubj plaques,form
R7204 T10774 T10772 aux to,form
R7205 T10775 T10751 punct .,observe
R7206 T10777 T10778 det This,finding
R7207 T10778 T10780 nsubj finding,indicates
R7208 T10779 T10778 amod latter,finding
R7209 T10781 T10782 mark that,is
R7210 T10782 T10780 ccomp is,indicates
R7211 T10783 T10782 prep compared,is
R7212 T10784 T10783 prep to,compared
R7213 T10785 T10786 amod other,aggregates
R7214 T10786 T10784 pobj aggregates,to
R7215 T10787 T10788 npadvmod disease,associated
R7216 T10788 T10786 amod associated,aggregates
R7217 T10789 T10788 punct -,associated
R7218 T10790 T10786 compound protein,aggregates
R7219 T10791 T10792 amod such,as
R7220 T10792 T10786 prep as,aggregates
R7221 T10793 T10794 compound mutant,huntingtin
R7222 T10794 T10792 pobj huntingtin,as
R7223 T10795 T10794 punct ", ",huntingtin
R7224 T10796 T10797 dep which,clear
R7225 T10797 T10794 relcl clear,huntingtin
R7226 T10798 T10797 prep in,clear
R7227 T10799 T10800 amod less,3
R7228 T10800 T10802 nummod 3,mo
R7229 T10801 T10800 quantmod than,3
R7230 T10802 T10798 pobj mo,in
R7231 T10803 T10804 punct [,32
R7232 T10804 T10797 parataxis 32,clear
R7233 T10805 T10804 punct ],32
R7234 T10806 T10782 punct ", ",is
R7235 T10807 T10808 det the,disaggregation
R7236 T10808 T10782 nsubj disaggregation,is
R7237 T10809 T10808 prep of,disaggregation
R7238 T10810 T10811 amod extracellular,amyloid
R7239 T10811 T10809 pobj amyloid,of
R7240 T10812 T10813 advmod relatively,slow
R7241 T10813 T10782 acomp slow,is
R7242 T10814 T10780 punct .,indicates
R7243 T10816 T10817 advmod Notably,show
R7244 T10818 T10817 punct ", ",show
R7245 T10819 T10820 amod pharmaceutical,inhibitors
R7246 T10820 T10817 nsubj inhibitors,show
R7247 T10821 T10822 punct γ,secretase
R7248 T10822 T10820 compound secretase,inhibitors
R7249 T10823 T10822 punct -,secretase
R7250 T10824 T10820 acl published,inhibitors
R7251 T10825 T10824 prep to,published
R7252 T10826 T10825 pobj date,to
R7253 T10827 T10828 advmod less,strict
R7254 T10828 T10829 amod strict,regulation
R7255 T10829 T10817 dobj regulation,show
R7256 T10830 T10829 prep of,regulation
R7257 T10831 T10832 compound Aβ,production
R7258 T10832 T10830 pobj production,of
R7259 T10833 T10829 prep following,regulation
R7260 T10834 T10835 amod chronic,administration
R7261 T10835 T10833 pobj administration,following
R7262 T10836 T10837 mark than,attained
R7263 T10837 T10829 advcl attained,regulation
R7264 T10838 T10837 nsubj we,attained
R7265 T10839 T10837 aux have,attained
R7266 T10840 T10837 advmod here,attained
R7267 T10841 T10817 punct .,show
R7268 T10843 T10844 nummod Two,compounds
R7269 T10844 T10846 nsubj compounds,show
R7270 T10845 T10844 amod independent,compounds
R7271 T10847 T10844 acl tested,compounds
R7272 T10848 T10847 prep in,tested
R7273 T10849 T10850 npadvmod Tg2576,transgenic
R7274 T10850 T10859 amod transgenic,mice
R7275 T10851 T10852 punct [,33
R7276 T10852 T10849 parataxis 33,Tg2576
R7277 T10853 T10852 punct ],33
R7278 T10854 T10849 cc and,Tg2576
R7279 T10855 T10849 conj TgCRND8,Tg2576
R7280 T10856 T10857 punct [,34
R7281 T10857 T10855 parataxis 34,TgCRND8
R7282 T10858 T10857 punct ],34
R7283 T10859 T10848 pobj mice,in
R7284 T10860 T10861 neg no,85
R7285 T10861 T10864 nummod 85,%
R7286 T10862 T10861 amod more,85
R7287 T10863 T10861 quantmod than,85
R7288 T10864 T10865 compound %,suppression
R7289 T10865 T10846 dobj suppression,show
R7290 T10866 T10865 prep of,suppression
R7291 T10867 T10868 compound Aβ40,levels
R7292 T10868 T10866 pobj levels,of
R7293 T10869 T10865 punct ", ",suppression
R7294 T10870 T10865 cc and,suppression
R7295 T10871 T10872 advmod where,measured
R7296 T10872 T10873 advcl measured,suppression
R7297 T10873 T10865 conj suppression,suppression
R7298 T10874 T10873 punct ", ",suppression
R7299 T10875 T10876 advmod even,less
R7300 T10876 T10873 amod less,suppression
R7301 T10877 T10873 prep of,suppression
R7302 T10878 T10877 pobj Aβ42,of
R7303 T10879 T10880 punct (,%
R7304 T10880 T10878 parataxis %,Aβ42
R7305 T10881 T10882 advmod approximately,60
R7306 T10882 T10880 nummod 60,%
R7307 T10883 T10880 punct ),%
R7308 T10884 T10885 punct [,36
R7309 T10885 T10846 parataxis 36,show
R7310 T10886 T10885 nummod 35,36
R7311 T10887 T10885 punct ",",36
R7312 T10888 T10885 punct ],36
R7313 T10889 T10846 punct .,show
R7314 T10891 T10892 advmod Thus,achieved
R7315 T10893 T10892 punct ", ",achieved
R7316 T10894 T10895 advmod even,after
R7317 T10895 T10892 prep after,achieved
R7318 T10896 T10895 pcomp accounting,after
R7319 T10897 T10896 prep for,accounting
R7320 T10898 T10899 det the,levels
R7321 T10899 T10897 pobj levels,for
R7322 T10900 T10901 advmod much,higher
R7323 T10901 T10899 amod higher,levels
R7324 T10902 T10899 compound APP,levels
R7325 T10903 T10899 compound expression,levels
R7326 T10904 T10899 prep in,levels
R7327 T10905 T10906 poss our,mice
R7328 T10906 T10904 pobj mice,in
R7329 T10907 T10899 prep than,levels
R7330 T10908 T10907 prep in,than
R7331 T10909 T10910 det the,lines
R7332 T10910 T10908 pobj lines,in
R7333 T10911 T10910 nmod Tg2576,lines
R7334 T10912 T10911 cc and,Tg2576
R7335 T10913 T10911 conj TgCRND8,Tg2576
R7336 T10914 T10892 punct ", ",achieved
R7337 T10915 T10892 nsubj we,achieved
R7338 T10916 T10892 aux have,achieved
R7339 T10917 T10918 advmod better,suppression
R7340 T10918 T10892 dobj suppression,achieved
R7341 T10919 T10918 amod absolute,suppression
R7342 T10920 T10918 prep of,suppression
R7343 T10921 T10922 compound Aβ,production
R7344 T10922 T10920 pobj production,of
R7345 T10923 T10918 prep with,suppression
R7346 T10924 T10925 det the,system
R7347 T10925 T10923 pobj system,with
R7348 T10926 T10927 compound tet,off
R7349 T10927 T10925 compound off,system
R7350 T10928 T10927 punct -,off
R7351 T10929 T10930 mark than,is
R7352 T10930 T10918 advcl is,suppression
R7353 T10931 T10930 advmod currently,is
R7354 T10932 T10930 acomp possible,is
R7355 T10933 T10930 prep with,is
R7356 T10934 T10935 amod published,inhibitors
R7357 T10935 T10933 pobj inhibitors,with
R7358 T10936 T10937 punct γ,secretase
R7359 T10937 T10935 compound secretase,inhibitors
R7360 T10938 T10937 punct -,secretase
R7361 T10939 T10892 punct .,achieved
R7362 T10941 T10942 mark Since,are
R7363 T10942 T10950 advcl are,provides
R7364 T10943 T10944 advmod even,agents
R7365 T10944 T10942 nsubj agents,are
R7366 T10945 T10944 det the,agents
R7367 T10946 T10947 advmod most,advanced
R7368 T10947 T10944 amod advanced,agents
R7369 T10948 T10944 amod future,agents
R7370 T10949 T10944 amod pharmaceutical,agents
R7371 T10951 T10942 acomp unlikely,are
R7372 T10952 T10953 aux to,attain
R7373 T10953 T10951 xcomp attain,unlikely
R7374 T10954 T10955 advmod more,complete
R7375 T10955 T10956 amod complete,control
R7376 T10956 T10953 dobj control,attain
R7377 T10957 T10956 prep of,control
R7378 T10958 T10959 compound Aβ,production
R7379 T10959 T10957 pobj production,of
R7380 T10960 T10961 mark than,achieved
R7381 T10961 T10956 advcl achieved,control
R7382 T10962 T10961 advmod here,achieved
R7383 T10963 T10950 punct ", ",provides
R7384 T10964 T10965 det this,system
R7385 T10965 T10950 nsubj system,provides
R7386 T10966 T10967 det a,test
R7387 T10967 T10950 dobj test,provides
R7388 T10968 T10967 amod salient,test
R7389 T10969 T10967 prep of,test
R7390 T10970 T10971 amod therapeutic,intervention
R7391 T10971 T10969 pobj intervention,of
R7392 T10972 T10971 prep with,intervention
R7393 T10973 T10974 npadvmod Aβ,lowering
R7394 T10974 T10976 amod lowering,compounds
R7395 T10975 T10974 punct -,lowering
R7396 T10976 T10972 pobj compounds,with
R7397 T10977 T10950 punct .,provides
R7398 T10979 T10980 mark Although,arrested
R7399 T10980 T10988 advcl arrested,found
R7400 T10981 T10982 det the,progression
R7401 T10982 T10980 nsubjpass progression,arrested
R7402 T10983 T10982 prep of,progression
R7403 T10984 T10985 compound amyloid,deposition
R7404 T10985 T10983 pobj deposition,of
R7405 T10986 T10980 auxpass was,arrested
R7406 T10987 T10980 advmod sharply,arrested
R7407 T10989 T10980 agent by,arrested
R7408 T10990 T10991 det this,approach
R7409 T10991 T10989 pobj approach,by
R7410 T10992 T10988 punct ", ",found
R7411 T10993 T10988 nsubj we,found
R7412 T10994 T10995 mark that,remained
R7413 T10995 T10988 ccomp remained,found
R7414 T10996 T10997 det a,burden
R7415 T10997 T10995 nsubj burden,remained
R7416 T10998 T10997 amod substantial,burden
R7417 T10999 T10997 compound amyloid,burden
R7418 T11000 T11001 advmod even,after
R7419 T11001 T10995 prep after,remained
R7420 T11002 T11003 amod long,periods
R7421 T11003 T11001 pobj periods,after
R7422 T11004 T11003 prep of,periods
R7423 T11005 T11006 compound transgene,suppression
R7424 T11006 T11004 pobj suppression,of
R7425 T11007 T10988 punct .,found
R7426 T11009 T11010 nsubj We,examined
R7427 T11011 T11012 det a,number
R7428 T11012 T11010 dobj number,examined
R7429 T11013 T11012 amod small,number
R7430 T11014 T11012 prep of,number
R7431 T11015 T11014 pobj animals,of
R7432 T11016 T11010 prep after,examined
R7433 T11017 T11018 nummod 12,mo
R7434 T11018 T11016 pobj mo,after
R7435 T11019 T11018 prep of,mo
R7436 T11020 T11021 compound dox,treatment
R7437 T11021 T11019 pobj treatment,of
R7438 T11022 T11021 punct (,treatment
R7439 T11023 T11021 acl beginning,treatment
R7440 T11024 T11023 prep at,beginning
R7441 T11025 T11026 nummod 6,mo
R7442 T11026 T11024 pobj mo,at
R7443 T11027 T11026 prep of,mo
R7444 T11028 T11027 pobj age,of
R7445 T11029 T11021 punct ),treatment
R7446 T11030 T11010 punct ", ",examined
R7447 T11031 T11010 cc and,examined
R7448 T11032 T11010 conj found,examined
R7449 T11033 T11034 mark that,were
R7450 T11034 T11032 ccomp were,found
R7451 T11035 T11036 compound amyloid,deposits
R7452 T11036 T11034 nsubj deposits,were
R7453 T11037 T11034 advmod still,were
R7454 T11038 T11039 advmod relatively,abundant
R7455 T11039 T11034 acomp abundant,were
R7456 T11040 T11010 punct .,examined
R7457 T11042 T11043 amod Longer,term
R7458 T11043 T11045 compound term,treatments
R7459 T11044 T11043 punct -,term
R7460 T11045 T11046 nsubj treatments,are
R7461 T11047 T11046 advmod now,are
R7462 T11048 T11046 prep in,are
R7463 T11049 T11048 pobj progress,in
R7464 T11050 T11046 punct .,are
R7465 T11052 T11053 prep At,showed
R7466 T11054 T11055 det the,interval
R7467 T11055 T11052 pobj interval,At
R7468 T11056 T11055 amod latest,interval
R7469 T11057 T11055 compound treatment,interval
R7470 T11058 T11055 acl analyzed,interval
R7471 T11059 T11058 agent by,analyzed
R7472 T11060 T11059 pobj ELISA,by
R7473 T11061 T11053 punct ", ",showed
R7474 T11062 T11053 nsubj animals,showed
R7475 T11063 T11062 acl administered,animals
R7476 T11064 T11063 dobj dox,administered
R7477 T11065 T11063 prep for,administered
R7478 T11066 T11067 nummod 6,mo
R7479 T11067 T11065 pobj mo,for
R7480 T11068 T11069 amod elevated,levels
R7481 T11069 T11053 dobj levels,showed
R7482 T11070 T11069 prep of,levels
R7483 T11071 T11072 npadvmod PBS,soluble
R7484 T11072 T11074 amod soluble,Aβ
R7485 T11073 T11072 punct -,soluble
R7486 T11074 T11070 pobj Aβ,of
R7487 T11075 T11076 punct (,see
R7488 T11076 T11074 parataxis see,Aβ
R7489 T11077 T11076 dobj Figure,see
R7490 T11078 T11077 nummod 5,Figure
R7491 T11079 T11076 punct ),see
R7492 T11080 T11081 dep that,interpreted
R7493 T11081 T11069 relcl interpreted,levels
R7494 T11082 T11081 aux could,interpreted
R7495 T11083 T11081 auxpass be,interpreted
R7496 T11084 T11081 prep as,interpreted
R7497 T11085 T11086 det an,indication
R7498 T11086 T11084 pobj indication,as
R7499 T11087 T11088 mark that,releasing
R7500 T11088 T11086 acl releasing,indication
R7501 T11089 T11090 det the,plaques
R7502 T11090 T11088 nsubj plaques,releasing
R7503 T11091 T11088 aux are,releasing
R7504 T11092 T11088 advmod slowly,releasing
R7505 T11093 T11088 dobj peptide,releasing
R7506 T11094 T11093 punct (,peptide
R7507 T11095 T11093 cc or,peptide
R7508 T11096 T11097 amod oligomeric,Aβ
R7509 T11097 T11093 conj Aβ,peptide
R7510 T11098 T11097 punct ),Aβ
R7511 T11099 T11088 prep into,releasing
R7512 T11100 T11101 det the,pool
R7513 T11101 T11099 pobj pool,into
R7514 T11102 T11101 amod soluble,pool
R7515 T11103 T11088 cc and,releasing
R7516 T11104 T11105 aux might,dissolve
R7517 T11105 T11088 conj dissolve,releasing
R7518 T11106 T11105 advmod eventually,dissolve
R7519 T11107 T11053 punct .,showed
R7520 T11109 T11110 mark Whether,result
R7521 T11110 T11124 csubj result,is
R7522 T11111 T11110 csubj inhibiting,result
R7523 T11112 T11113 compound Aβ,production
R7524 T11113 T11111 dobj production,inhibiting
R7525 T11114 T11111 advmod longer,inhibiting
R7526 T11115 T11114 prep than,longer
R7527 T11116 T11117 nummod 6,mo
R7528 T11117 T11115 pobj mo,than
R7529 T11118 T11116 punct (,6
R7530 T11119 T11116 cc or,6
R7531 T11120 T11116 conj 12,6
R7532 T11121 T11117 punct ),mo
R7533 T11122 T11110 aux may,result
R7534 T11123 T11110 advmod ultimately,result
R7535 T11124 T11129 ccomp is,limits
R7536 T11125 T11110 prep in,result
R7537 T11126 T11125 pobj clearance,in
R7538 T11127 T11126 prep of,clearance
R7539 T11128 T11127 pobj amyloid,of
R7540 T11130 T11124 prep under,is
R7541 T11131 T11130 pobj investigation,under
R7542 T11132 T11129 punct ;,limits
R7543 T11133 T11129 advmod unfortunately,limits
R7544 T11134 T11129 punct ", ",limits
R7545 T11135 T11136 det the,span
R7546 T11136 T11129 nsubj span,limits
R7547 T11137 T11136 compound life,span
R7548 T11138 T11136 prep of,span
R7549 T11139 T11140 det the,model
R7550 T11140 T11138 pobj model,of
R7551 T11141 T11129 advmod eventually,limits
R7552 T11142 T11143 det this,experiment
R7553 T11143 T11129 dobj experiment,limits
R7554 T11144 T11129 punct .,limits
R7555 T11146 T11147 nsubj Therapeutics,have
R7556 T11148 T11146 acl used,Therapeutics
R7557 T11149 T11148 prep in,used
R7558 T11150 T11149 pobj humans,in
R7559 T11151 T11147 aux will,have
R7560 T11152 T11153 advmod considerably,more
R7561 T11153 T11154 amod more,time
R7562 T11154 T11147 dobj time,have
R7563 T11155 T11156 aux to,act
R7564 T11156 T11154 advcl act,time
R7565 T11157 T11158 mark than,is
R7566 T11158 T11154 advcl is,time
R7567 T11159 T11158 acomp possible,is
R7568 T11160 T11158 prep within,is
R7569 T11161 T11162 det the,span
R7570 T11162 T11160 pobj span,within
R7571 T11163 T11162 compound life,span
R7572 T11164 T11162 prep of,span
R7573 T11165 T11166 compound rodent,models
R7574 T11166 T11164 pobj models,of
R7575 T11167 T11147 punct .,have
R7576 T11169 T11170 amod Long,term
R7577 T11170 T11172 compound term,treatments
R7578 T11171 T11170 punct -,term
R7579 T11172 T11173 nsubj treatments,be
R7580 T11174 T11173 aux would,be
R7581 T11175 T11173 advmod certainly,be
R7582 T11176 T11173 acomp possible,be
R7583 T11177 T11173 cc and,be
R7584 T11178 T11179 aux could,be
R7585 T11179 T11173 conj be,be
R7586 T11180 T11181 det a,key
R7587 T11181 T11179 attr key,be
R7588 T11182 T11181 prep to,key
R7589 T11183 T11184 amod effective,therapy
R7590 T11184 T11182 pobj therapy,to
R7591 T11185 T11173 punct .,be
R7592 T11187 T11188 advmod Overall,interpret
R7593 T11189 T11188 punct ", ",interpret
R7594 T11190 T11188 advmod however,interpret
R7595 T11191 T11188 punct ", ",interpret
R7596 T11192 T11188 nsubj we,interpret
R7597 T11193 T11194 poss our,findings
R7598 T11194 T11188 dobj findings,interpret
R7599 T11195 T11188 prep as,interpret
R7600 T11196 T11195 pobj evidence,as
R7601 T11197 T11198 mark that,reverse
R7602 T11198 T11196 acl reverse,evidence
R7603 T11199 T11200 compound AD,therapies
R7604 T11200 T11198 nsubj therapies,reverse
R7605 T11201 T11202 dep that,lower
R7606 T11202 T11200 relcl lower,therapies
R7607 T11203 T11202 advmod significantly,lower
R7608 T11204 T11205 det the,production
R7609 T11205 T11202 dobj production,lower
R7610 T11206 T11205 prep of,production
R7611 T11207 T11206 pobj Aβ,of
R7612 T11208 T11202 punct (,lower
R7613 T11209 T11202 prep by,lower
R7614 T11210 T11211 preconj either,inhibiting
R7615 T11211 T11209 pcomp inhibiting,by
R7616 T11212 T11213 compound secretase,activity
R7617 T11213 T11211 dobj activity,inhibiting
R7618 T11214 T11211 cc or,inhibiting
R7619 T11215 T11211 conj inhibiting,inhibiting
R7620 T11216 T11217 compound APP,expression
R7621 T11217 T11215 dobj expression,inhibiting
R7622 T11218 T11202 punct ),lower
R7623 T11219 T11198 aux may,reverse
R7624 T11220 T11198 neg not,reverse
R7625 T11221 T11198 advmod quickly,reverse
R7626 T11222 T11223 amod preexisting,pathology
R7627 T11223 T11198 dobj pathology,reverse
R7628 T11224 T11198 punct ", ",reverse
R7629 T11225 T11198 cc but,reverse
R7630 T11226 T11227 aux should,halt
R7631 T11227 T11198 conj halt,reverse
R7632 T11228 T11227 advmod effectively,halt
R7633 T11229 T11230 amod further,deposition
R7634 T11230 T11227 dobj deposition,halt
R7635 T11231 T11230 prep of,deposition
R7636 T11232 T11231 pobj amyloid,of
R7637 T11233 T11188 punct .,interpret
R7638 T11235 T11236 prep In,remembered
R7639 T11237 T11235 pcomp interpreting,In
R7640 T11238 T11239 poss our,study
R7641 T11239 T11237 dobj study,interpreting
R7642 T11240 T11236 punct ", ",remembered
R7643 T11241 T11236 nsubjpass it,remembered
R7644 T11242 T11236 aux should,remembered
R7645 T11243 T11236 auxpass be,remembered
R7646 T11244 T11245 mark that,are
R7647 T11245 T11236 ccomp are,remembered
R7648 T11246 T11247 det the,plaques
R7649 T11247 T11245 nsubj plaques,are
R7650 T11248 T11247 amod earliest,plaques
R7651 T11249 T11250 aux to,appear
R7652 T11250 T11247 advcl appear,plaques
R7653 T11251 T11250 prep in,appear
R7654 T11252 T11253 det these,mice
R7655 T11253 T11251 pobj mice,in
R7656 T11254 T11247 punct ", ",plaques
R7657 T11255 T11247 prep like,plaques
R7658 T11256 T11257 amod other,transgenics
R7659 T11257 T11255 pobj transgenics,like
R7660 T11258 T11257 compound APP,transgenics
R7661 T11259 T11257 acl harboring,transgenics
R7662 T11260 T11261 det the,mutation
R7663 T11261 T11259 dobj mutation,harboring
R7664 T11262 T11261 amod Swedish,mutation
R7665 T11263 T11264 punct [,27
R7666 T11264 T11259 parataxis 27,harboring
R7667 T11265 T11264 punct ],27
R7668 T11266 T11245 punct ", ",are
R7669 T11267 T11245 advmod predominantly,are
R7670 T11268 T11269 amod fibrillar,deposits
R7671 T11269 T11245 attr deposits,are
R7672 T11270 T11269 punct ", ",deposits
R7673 T11271 T11272 dep which,be
R7674 T11272 T11269 relcl be,deposits
R7675 T11273 T11272 aux may,be
R7676 T11274 T11275 advmod less,tractable
R7677 T11275 T11272 acomp tractable,be
R7678 T11276 T11275 prep than,tractable
R7679 T11277 T11278 det the,aggregates
R7680 T11278 T11276 pobj aggregates,than
R7681 T11279 T11278 amod diffuse,aggregates
R7682 T11280 T11278 acl thought,aggregates
R7683 T11281 T11282 aux to,come
R7684 T11282 T11280 xcomp come,thought
R7685 T11283 T11282 advmod first,come
R7686 T11284 T11282 prep in,come
R7687 T11285 T11286 det the,course
R7688 T11286 T11284 pobj course,in
R7689 T11287 T11286 prep of,course
R7690 T11288 T11289 det the,disease
R7691 T11289 T11287 pobj disease,of
R7692 T11290 T11289 amod human,disease
R7693 T11291 T11236 punct .,remembered
R7694 T11293 T11294 advmod However,suggest
R7695 T11295 T11294 punct ", ",suggest
R7696 T11296 T11297 poss our,data
R7697 T11297 T11294 nsubj data,suggest
R7698 T11298 T11299 mark that,cleared
R7699 T11299 T11294 ccomp cleared,suggest
R7700 T11300 T11301 mark once,formed
R7701 T11301 T11299 advcl formed,cleared
R7702 T11302 T11303 amod diffuse,deposits
R7703 T11303 T11301 nsubjpass deposits,formed
R7704 T11304 T11301 auxpass are,formed
R7705 T11305 T11301 prep in,formed
R7706 T11306 T11307 det these,mice
R7707 T11307 T11305 pobj mice,in
R7708 T11308 T11299 punct ", ",cleared
R7709 T11309 T11299 nsubjpass they,cleared
R7710 T11310 T11299 auxpass are,cleared
R7711 T11311 T11312 neg no,more
R7712 T11312 T11313 advmod more,easily
R7713 T11313 T11299 advmod easily,cleared
R7714 T11314 T11299 prep in,cleared
R7715 T11315 T11316 poss our,system
R7716 T11316 T11314 pobj system,in
R7717 T11317 T11299 prep than,cleared
R7718 T11318 T11319 amod cored,plaques
R7719 T11319 T11317 pobj plaques,than
R7720 T11320 T11321 punct (,see
R7721 T11321 T11299 parataxis see,cleared
R7722 T11322 T11323 compound Figure,S4
R7723 T11323 T11321 dobj S4,see
R7724 T11324 T11321 punct ),see
R7725 T11325 T11294 punct .,suggest
R7726 T11327 T11328 det An,consideration
R7727 T11328 T11330 nsubj consideration,is
R7728 T11329 T11328 amod additional,consideration
R7729 T11331 T11332 nsubj we,recognize
R7730 T11332 T11328 advcl recognize,consideration
R7731 T11333 T11334 mark that,continues
R7732 T11334 T11330 advcl continues,is
R7733 T11335 T11336 det a,amount
R7734 T11336 T11334 nsubj amount,continues
R7735 T11337 T11336 amod small,amount
R7736 T11338 T11336 prep of,amount
R7737 T11339 T11340 compound transgene,expression
R7738 T11340 T11338 pobj expression,of
R7739 T11341 T11334 prep in,continues
R7740 T11342 T11343 det the,presence
R7741 T11343 T11341 pobj presence,in
R7742 T11344 T11343 prep of,presence
R7743 T11345 T11344 pobj dox,of
R7744 T11346 T11334 cc and,continues
R7745 T11347 T11348 mark that,continues
R7746 T11348 T11334 conj continues,continues
R7747 T11349 T11350 amod endogenous,Aβ
R7748 T11350 T11348 nsubj Aβ,continues
R7749 T11351 T11350 compound mouse,Aβ
R7750 T11352 T11353 aux to,produced
R7751 T11353 T11348 xcomp produced,continues
R7752 T11354 T11353 auxpass be,produced
R7753 T11355 T11330 punct .,is
R7754 T11357 T11358 nsubj It,is
R7755 T11359 T11358 acomp possible,is
R7756 T11360 T11361 mark that,are
R7757 T11361 T11358 ccomp are,is
R7758 T11362 T11363 det the,levels
R7759 T11363 T11361 nsubj levels,are
R7760 T11364 T11363 amod combined,levels
R7761 T11365 T11363 amod low,levels
R7762 T11366 T11363 prep of,levels
R7763 T11367 T11368 amod endogenous,Aβ
R7764 T11368 T11370 nmod Aβ,peptide
R7765 T11369 T11368 nmod mouse,Aβ
R7766 T11370 T11366 pobj peptide,of
R7767 T11371 T11368 cc and,Aβ
R7768 T11372 T11373 amod nonsuppressed,human
R7769 T11373 T11368 conj human,Aβ
R7770 T11374 T11361 acomp sufficient,are
R7771 T11375 T11376 aux to,maintain
R7772 T11376 T11374 xcomp maintain,sufficient
R7773 T11377 T11378 amod existing,deposits
R7774 T11378 T11376 dobj deposits,maintain
R7775 T11379 T11358 punct .,is
R7776 T11381 T11382 advmod However,are
R7777 T11383 T11382 punct ", ",are
R7778 T11384 T11385 det these,levels
R7779 T11385 T11382 nsubj levels,are
R7780 T11386 T11385 amod low,levels
R7781 T11387 T11385 prep of,levels
R7782 T11388 T11387 pobj peptide,of
R7783 T11389 T11382 neg not,are
R7784 T11390 T11382 acomp sufficient,are
R7785 T11391 T11392 aux to,induce
R7786 T11392 T11390 xcomp induce,sufficient
R7787 T11393 T11394 amod new,formation
R7788 T11394 T11392 dobj formation,induce
R7789 T11395 T11394 compound amyloid,formation
R7790 T11396 T11382 punct ", ",are
R7791 T11397 T11398 mark as,develop
R7792 T11398 T11382 advcl develop,are
R7793 T11399 T11400 nmod CaMKIIα,ind
R7794 T11400 T11406 compound ind,mice
R7795 T11401 T11400 punct -,ind
R7796 T11402 T11400 nmod tTA,ind
R7797 T11403 T11400 punct ×,ind
R7798 T11404 T11400 compound tetAPPswe,ind
R7799 T11405 T11400 punct /,ind
R7800 T11406 T11398 nsubj mice,develop
R7801 T11407 T11406 acl raised,mice
R7802 T11408 T11407 prep on,raised
R7803 T11409 T11408 pobj dox,on
R7804 T11410 T11407 prep for,raised
R7805 T11411 T11412 quantmod up,a
R7806 T11412 T11414 nummod a,year
R7807 T11413 T11412 quantmod to,a
R7808 T11414 T11410 pobj year,for
R7809 T11415 T11398 aux do,develop
R7810 T11416 T11398 neg not,develop
R7811 T11417 T11418 compound amyloid,lesions
R7812 T11418 T11398 dobj lesions,develop
R7813 T11419 T11420 punct (,shown
R7814 T11420 T11398 parataxis shown,develop
R7815 T11421 T11420 nsubj data,shown
R7816 T11422 T11420 neg not,shown
R7817 T11423 T11420 punct ),shown
R7818 T11424 T11382 punct .,are
R7819 T11426 T11427 nsubj It,is
R7820 T11428 T11427 advmod also,is
R7821 T11429 T11427 acomp clear,is
R7822 T11430 T11431 mark that,raised
R7823 T11431 T11427 ccomp raised,is
R7824 T11432 T11431 prep in,raised
R7825 T11433 T11434 det this,system
R7826 T11434 T11432 pobj system,in
R7827 T11435 T11434 amod genetic,system
R7828 T11436 T11431 punct ", ",raised
R7829 T11437 T11431 nsubj we,raised
R7830 T11438 T11431 aux have,raised
R7831 T11439 T11440 det the,production
R7832 T11440 T11431 dobj production,raised
R7833 T11441 T11440 prep of,production
R7834 T11442 T11441 pobj Aβ,of
R7835 T11443 T11431 prep to,raised
R7836 T11444 T11443 pobj levels,to
R7837 T11445 T11446 neg not,found
R7838 T11446 T11444 acl found,levels
R7839 T11447 T11446 prep in,found
R7840 T11448 T11447 pobj humans,in
R7841 T11449 T11450 aux to,accelerate
R7842 T11450 T11431 advcl accelerate,raised
R7843 T11451 T11450 dobj pathology,accelerate
R7844 T11452 T11450 prep into,accelerate
R7845 T11453 T11454 det an,frame
R7846 T11454 T11452 pobj frame,into
R7847 T11455 T11456 advmod experimentally,feasible
R7848 T11456 T11454 amod feasible,frame
R7849 T11457 T11454 compound time,frame
R7850 T11458 T11427 punct .,is
R7851 T11460 T11461 det This,system
R7852 T11461 T11462 nsubj system,allowed
R7853 T11462 T11463 ccomp allowed,favored
R7854 T11464 T11465 nsubj us,create
R7855 T11465 T11462 ccomp create,allowed
R7856 T11466 T11465 aux to,create
R7857 T11467 T11468 det an,differential
R7858 T11468 T11465 dobj differential,create
R7859 T11469 T11470 advmod approximately,20-fold
R7860 T11470 T11468 amod 20-fold,differential
R7861 T11471 T11468 prep between,differential
R7862 T11472 T11473 nmod APP,Aβ
R7863 T11473 T11475 nmod Aβ,rates
R7864 T11474 T11473 punct /,Aβ
R7865 T11475 T11471 pobj rates,between
R7866 T11476 T11475 amod synthetic,rates
R7867 T11477 T11465 prep before,create
R7868 T11478 T11477 cc and,before
R7869 T11479 T11477 conj after,before
R7870 T11480 T11479 pobj treatment,after
R7871 T11481 T11463 punct ", ",favored
R7872 T11482 T11463 advmod yet,favored
R7873 T11483 T11484 det the,equilibrium
R7874 T11484 T11463 nsubj equilibrium,favored
R7875 T11485 T11486 advmod in,vivo
R7876 T11486 T11484 amod vivo,equilibrium
R7877 T11487 T11484 prep between,equilibrium
R7878 T11488 T11489 amod aggregated,states
R7879 T11489 T11487 pobj states,between
R7880 T11490 T11488 cc and,aggregated
R7881 T11491 T11488 conj disaggregated,aggregated
R7882 T11492 T11489 prep of,states
R7883 T11493 T11492 pobj Aβ,of
R7884 T11494 T11463 advmod still,favored
R7885 T11495 T11496 det the,maintenance
R7886 T11496 T11463 dobj maintenance,favored
R7887 T11497 T11496 prep of,maintenance
R7888 T11498 T11499 compound amyloid,deposits
R7889 T11499 T11497 pobj deposits,of
R7890 T11500 T11463 punct .,favored
R7891 T11502 T11503 prep In,seems
R7892 T11504 T11505 poss our,opinion
R7893 T11505 T11502 pobj opinion,In
R7894 T11506 T11503 punct ", ",seems
R7895 T11507 T11503 nsubj it,seems
R7896 T11508 T11503 oprd unlikely,seems
R7897 T11509 T11510 mark that,be
R7898 T11510 T11503 ccomp be,seems
R7899 T11511 T11512 compound amyloid,deposits
R7900 T11512 T11510 nsubj deposits,be
R7901 T11513 T11512 prep in,deposits
R7902 T11514 T11515 amod human,brain
R7903 T11515 T11513 pobj brain,in
R7904 T11516 T11510 aux would,be
R7905 T11517 T11510 advmod inherently,be
R7906 T11518 T11519 advmod any,stable
R7907 T11519 T11510 acomp stable,be
R7908 T11520 T11519 advmod less,stable
R7909 T11521 T11519 prep than,stable
R7910 T11522 T11521 pobj those,than
R7911 T11523 T11522 acl formed,those
R7912 T11524 T11523 prep in,formed
R7913 T11525 T11526 compound mouse,brain
R7914 T11526 T11524 pobj brain,in
R7915 T11527 T11503 punct .,seems
R7916 T11529 T11530 advmod However,harbor
R7917 T11531 T11530 punct ", ",harbor
R7918 T11532 T11533 det the,brain
R7919 T11533 T11530 nsubj brain,harbor
R7920 T11534 T11533 amod human,brain
R7921 T11535 T11530 aux may,harbor
R7922 T11536 T11537 compound clearance,mechanisms
R7923 T11537 T11530 dobj mechanisms,harbor
R7924 T11538 T11539 neg not,shared
R7925 T11539 T11537 acl shared,mechanisms
R7926 T11540 T11539 agent by,shared
R7927 T11541 T11540 pobj mice,by
R7928 T11542 T11543 dep that,allow
R7929 T11543 T11537 relcl allow,mechanisms
R7930 T11544 T11543 aux would,allow
R7931 T11545 T11546 advmod more,efficient
R7932 T11546 T11547 amod efficient,removal
R7933 T11547 T11543 dobj removal,allow
R7934 T11548 T11547 prep of,removal
R7935 T11549 T11550 amod preexisting,amyloid
R7936 T11550 T11548 pobj amyloid,of
R7937 T11551 T11530 punct .,harbor
R7938 T11553 T11554 nummod One,mechanism
R7939 T11554 T11556 nsubj mechanism,is
R7940 T11555 T11554 amod potential,mechanism
R7941 T11557 T11558 prep by,removed
R7942 T11558 T11554 relcl removed,mechanism
R7943 T11559 T11557 pobj which,by
R7944 T11560 T11558 nsubjpass amyloid,removed
R7945 T11561 T11558 aux may,removed
R7946 T11562 T11558 auxpass be,removed
R7947 T11563 T11564 advmod more,efficiently
R7948 T11564 T11558 advmod efficiently,removed
R7949 T11565 T11558 prep in,removed
R7950 T11566 T11567 det the,disease
R7951 T11567 T11565 pobj disease,in
R7952 T11568 T11567 amod human,disease
R7953 T11569 T11558 prep than,removed
R7954 T11570 T11569 prep in,than
R7955 T11571 T11572 det the,models
R7956 T11572 T11570 pobj models,in
R7957 T11573 T11572 compound mouse,models
R7958 T11574 T11556 prep through,is
R7959 T11575 T11576 amod microglial,phagocytosis
R7960 T11576 T11574 pobj phagocytosis,through
R7961 T11577 T11556 punct .,is
R7962 T11579 T11580 amod Resident,microglia
R7963 T11580 T11581 nsubj microglia,localize
R7964 T11582 T11580 prep in,microglia
R7965 T11583 T11584 amod transgenic,models
R7966 T11584 T11582 pobj models,in
R7967 T11585 T11584 compound mouse,models
R7968 T11586 T11581 prep to,localize
R7969 T11587 T11586 pobj tissue,to
R7970 T11588 T11587 acl surrounding,tissue
R7971 T11589 T11588 dobj plaques,surrounding
R7972 T11590 T11581 cc but,localize
R7973 T11591 T11581 conj show,localize
R7974 T11592 T11593 amod little,evidence
R7975 T11593 T11591 dobj evidence,show
R7976 T11594 T11593 prep of,evidence
R7977 T11595 T11596 compound amyloid,engulfment
R7978 T11596 T11594 pobj engulfment,of
R7979 T11597 T11598 punct [,37
R7980 T11598 T11591 parataxis 37,show
R7981 T11599 T11600 punct –,40
R7982 T11600 T11598 prep 40,37
R7983 T11601 T11598 punct ],37
R7984 T11602 T11581 punct .,localize
R7985 T11604 T11605 prep In,show
R7986 T11606 T11604 pobj contrast,In
R7987 T11607 T11605 punct ", ",show
R7988 T11608 T11605 nsubj microglia,show
R7989 T11609 T11608 acl surrounding,microglia
R7990 T11610 T11611 compound amyloid,plaques
R7991 T11611 T11609 dobj plaques,surrounding
R7992 T11612 T11609 prep in,surrounding
R7993 T11613 T11614 amod human,brain
R7994 T11614 T11612 pobj brain,in
R7995 T11615 T11616 det a,state
R7996 T11616 T11605 dobj state,show
R7997 T11617 T11618 advmod much,higher
R7998 T11618 T11616 amod higher,state
R7999 T11619 T11616 prep of,state
R8000 T11620 T11619 pobj activation,of
R8001 T11621 T11605 prep with,show
R8002 T11622 T11623 amod greater,expression
R8003 T11623 T11621 pobj expression,with
R8004 T11624 T11623 prep of,expression
R8005 T11625 T11626 compound complement,receptor
R8006 T11626 T11624 pobj receptor,of
R8007 T11627 T11628 punct [,40
R8008 T11628 T11605 parataxis 40,show
R8009 T11629 T11628 punct ],40
R8010 T11630 T11605 punct .,show
R8011 T11632 T11633 advmod Thus,is
R8012 T11634 T11633 punct ", ",is
R8013 T11635 T11636 det the,role
R8014 T11636 T11633 nsubj role,is
R8015 T11637 T11636 prep of,role
R8016 T11638 T11637 pobj microglia,of
R8017 T11639 T11636 prep in,role
R8018 T11640 T11641 compound amyloid,metabolism
R8019 T11641 T11639 pobj metabolism,in
R8020 T11642 T11633 acomp minor,is
R8021 T11643 T11633 prep in,is
R8022 T11644 T11645 amod transgenic,models
R8023 T11645 T11643 pobj models,in
R8024 T11646 T11633 prep compared,is
R8025 T11647 T11646 prep to,compared
R8026 T11648 T11649 det the,condition
R8027 T11649 T11647 pobj condition,to
R8028 T11650 T11649 amod human,condition
R8029 T11651 T11633 punct .,is
R8030 T11653 T11654 advmod Somewhat,paradoxically
R8031 T11654 T11655 advmod paradoxically,demonstrate
R8032 T11656 T11655 punct ", ",demonstrate
R8033 T11657 T11658 amod several,studies
R8034 T11658 T11655 nsubj studies,demonstrate
R8035 T11659 T11655 advmod further,demonstrate
R8036 T11660 T11661 mark that,lowers
R8037 T11661 T11655 ccomp lowers,demonstrate
R8038 T11662 T11661 nsubj treatment,lowers
R8039 T11663 T11662 prep with,treatment
R8040 T11664 T11665 amod anti-inflammatory,drugs
R8041 T11665 T11663 pobj drugs,with
R8042 T11666 T11667 aux to,reduce
R8043 T11667 T11662 advcl reduce,treatment
R8044 T11668 T11669 amod microglial,activation
R8045 T11669 T11667 dobj activation,reduce
R8046 T11670 T11661 advmod actually,lowers
R8047 T11671 T11672 compound amyloid,load
R8048 T11672 T11661 dobj load,lowers
R8049 T11673 T11661 prep in,lowers
R8050 T11674 T11675 npadvmod APP,transgenic
R8051 T11675 T11676 amod transgenic,mice
R8052 T11676 T11673 pobj mice,in
R8053 T11677 T11661 punct ", ",lowers
R8054 T11678 T11661 advcl suggesting,lowers
R8055 T11679 T11680 det a,role
R8056 T11680 T11678 dobj role,suggesting
R8057 T11681 T11680 prep for,role
R8058 T11682 T11683 compound mouse,microglia
R8059 T11683 T11681 pobj microglia,for
R8060 T11684 T11680 prep in,role
R8061 T11685 T11686 det the,formation
R8062 T11686 T11684 pobj formation,in
R8063 T11687 T11686 cc and,formation
R8064 T11688 T11686 conj maintenance,formation
R8065 T11689 T11686 prep of,formation
R8066 T11690 T11691 compound amyloid,aggregates
R8067 T11691 T11689 pobj aggregates,of
R8068 T11692 T11693 punct [,41
R8069 T11693 T11661 parataxis 41,lowers
R8070 T11694 T11695 punct –,43
R8071 T11695 T11693 prep 43,41
R8072 T11696 T11693 punct ],41
R8073 T11697 T11655 punct .,demonstrate
R8074 T11699 T11700 advmod However,explained
R8075 T11701 T11700 punct ", ",explained
R8076 T11702 T11703 det this,outcome
R8077 T11703 T11700 nsubjpass outcome,explained
R8078 T11704 T11700 aux may,explained
R8079 T11705 T11700 auxpass be,explained
R8080 T11706 T11700 advmod alternatively,explained
R8081 T11707 T11700 agent by,explained
R8082 T11708 T11709 amod direct,effects
R8083 T11709 T11707 pobj effects,by
R8084 T11710 T11709 prep of,effects
R8085 T11711 T11712 amod many,drugs
R8086 T11712 T11710 pobj drugs,of
R8087 T11713 T11712 amod anti-inflammatory,drugs
R8088 T11714 T11709 prep on,effects
R8089 T11715 T11716 punct γ,secretase
R8090 T11716 T11718 compound secretase,cleavage
R8091 T11717 T11716 punct -,secretase
R8092 T11718 T11714 pobj cleavage,on
R8093 T11719 T11720 punct [,44
R8094 T11720 T11700 parataxis 44,explained
R8095 T11721 T11722 punct –,47
R8096 T11722 T11720 prep 47,44
R8097 T11723 T11720 punct ],44
R8098 T11724 T11700 punct .,explained
R8099 T11726 T11727 advmod Nonetheless,is
R8100 T11728 T11727 punct ", ",is
R8101 T11729 T11730 det the,role
R8102 T11730 T11727 nsubj role,is
R8103 T11731 T11730 prep of,role
R8104 T11732 T11731 pobj microglia,of
R8105 T11733 T11730 prep in,role
R8106 T11734 T11735 preconj both,condition
R8107 T11735 T11733 pobj condition,in
R8108 T11736 T11735 det the,condition
R8109 T11737 T11735 amod human,condition
R8110 T11738 T11735 cc and,condition
R8111 T11739 T11740 det the,models
R8112 T11740 T11735 conj models,condition
R8113 T11741 T11740 compound mouse,models
R8114 T11742 T11743 advmod poorly,understood
R8115 T11743 T11727 acomp understood,is
R8116 T11744 T11727 punct ", ",is
R8117 T11745 T11727 cc and,is
R8118 T11746 T11747 nsubj differences,lead
R8119 T11747 T11727 conj lead,is
R8120 T11748 T11746 prep in,differences
R8121 T11749 T11750 amod microglial,reactivity
R8122 T11750 T11748 pobj reactivity,in
R8123 T11751 T11746 prep between,differences
R8124 T11752 T11753 det the,two
R8125 T11753 T11751 pobj two,between
R8126 T11754 T11747 aux could,lead
R8127 T11755 T11747 prep to,lead
R8128 T11756 T11757 advmod significantly,faster
R8129 T11757 T11758 amod faster,clearance
R8130 T11758 T11755 pobj clearance,to
R8131 T11759 T11758 compound amyloid,clearance
R8132 T11760 T11758 prep in,clearance
R8133 T11761 T11762 det the,brains
R8134 T11762 T11760 pobj brains,in
R8135 T11763 T11762 prep of,brains
R8136 T11764 T11763 pobj patients,of
R8137 T11765 T11764 prep with,patients
R8138 T11766 T11765 pobj AD,with
R8139 T11767 T11768 mark than,observe
R8140 T11768 T11758 advcl observe,clearance
R8141 T11769 T11768 nsubj we,observe
R8142 T11770 T11768 prep in,observe
R8143 T11771 T11772 det the,mice
R8144 T11772 T11770 pobj mice,in
R8145 T11773 T11774 compound tet,off
R8146 T11774 T11772 compound off,mice
R8147 T11775 T11774 punct -,off
R8148 T11776 T11772 compound APP,mice
R8149 T11777 T11747 punct .,lead
R8150 T11779 T11780 prep Given,think
R8151 T11781 T11782 det the,role
R8152 T11782 T11779 pobj role,Given
R8153 T11783 T11784 advmod relatively,minor
R8154 T11784 T11782 amod minor,role
R8155 T11785 T11782 acl played,role
R8156 T11786 T11785 agent by,played
R8157 T11787 T11786 pobj microglia,by
R8158 T11788 T11785 prep in,played
R8159 T11789 T11790 amod other,models
R8160 T11790 T11788 pobj models,in
R8161 T11791 T11790 compound mouse,models
R8162 T11792 T11790 prep of,models
R8163 T11793 T11792 pobj amyloidosis,of
R8164 T11794 T11780 punct ", ",think
R8165 T11795 T11780 nsubj we,think
R8166 T11796 T11797 nsubj it,unlikely
R8167 T11797 T11780 advcl unlikely,think
R8168 T11798 T11799 mark that,influenced
R8169 T11799 T11797 advcl influenced,unlikely
R8170 T11800 T11801 det these,cells
R8171 T11801 T11799 nsubj cells,influenced
R8172 T11802 T11799 aux have,influenced
R8173 T11803 T11804 det the,rate
R8174 T11804 T11799 dobj rate,influenced
R8175 T11805 T11804 prep of,rate
R8176 T11806 T11807 compound amyloid,clearance
R8177 T11807 T11805 pobj clearance,of
R8178 T11808 T11799 prep in,influenced
R8179 T11809 T11810 det the,mice
R8180 T11810 T11808 pobj mice,in
R8181 T11811 T11812 compound tet,off
R8182 T11812 T11810 compound off,mice
R8183 T11813 T11812 punct -,off
R8184 T11814 T11810 compound APP,mice
R8185 T11815 T11780 punct .,think
R8186 T11817 T11818 advmod Even,so
R8187 T11818 T11819 advmod so,considered
R8188 T11820 T11819 punct ", ",considered
R8189 T11821 T11819 nsubj we,considered
R8190 T11822 T11823 det the,possibility
R8191 T11823 T11819 dobj possibility,considered
R8192 T11824 T11825 mark that,altered
R8193 T11825 T11823 acl altered,possibility
R8194 T11826 T11827 amod chronic,treatment
R8195 T11827 T11825 nsubj treatment,altered
R8196 T11828 T11827 compound dox,treatment
R8197 T11829 T11825 aux may,altered
R8198 T11830 T11825 aux have,altered
R8199 T11831 T11832 det the,state
R8200 T11832 T11825 dobj state,altered
R8201 T11833 T11832 compound activation,state
R8202 T11834 T11832 prep of,state
R8203 T11835 T11834 pobj microglia,of
R8204 T11836 T11825 prep in,altered
R8205 T11837 T11838 poss our,mice
R8206 T11838 T11836 pobj mice,in
R8207 T11839 T11838 amod treated,mice
R8208 T11840 T11819 punct .,considered
R8209 T11842 T11843 nsubj Dox,is
R8210 T11844 T11845 advmod structurally,similar
R8211 T11845 T11843 acomp similar,is
R8212 T11846 T11845 prep to,similar
R8213 T11847 T11846 pobj minocycline,to
R8214 T11848 T11847 punct ", ",minocycline
R8215 T11849 T11850 det a,drug
R8216 T11850 T11847 appos drug,minocycline
R8217 T11851 T11850 amod reported,drug
R8218 T11852 T11850 amod anti-inflammatory,drug
R8219 T11853 T11850 cc and,drug
R8220 T11854 T11850 conj inhibitor,drug
R8221 T11855 T11854 prep of,inhibitor
R8222 T11856 T11857 amod microglial,activation
R8223 T11857 T11855 pobj activation,of
R8224 T11858 T11859 punct [,48
R8225 T11859 T11843 parataxis 48,is
R8226 T11860 T11859 punct ],48
R8227 T11861 T11843 punct .,is
R8228 T11863 T11864 advmod However,expected
R8229 T11865 T11864 punct ", ",expected
R8230 T11866 T11867 mark if,have
R8231 T11867 T11864 advcl have,expected
R8232 T11868 T11867 nsubj dox,have
R8233 T11869 T11867 aux does,have
R8234 T11870 T11871 amod anti-inflammatory,activity
R8235 T11871 T11867 dobj activity,have
R8236 T11872 T11864 punct ", ",expected
R8237 T11873 T11864 advmod then,expected
R8238 T11874 T11864 punct ", ",expected
R8239 T11875 T11864 prep based,expected
R8240 T11876 T11875 prep on,based
R8241 T11877 T11878 amod previous,studies
R8242 T11878 T11876 pobj studies,on
R8243 T11879 T11878 prep with,studies
R8244 T11880 T11881 amod other,anti-inflammatories
R8245 T11881 T11879 pobj anti-inflammatories,with
R8246 T11882 T11864 punct ", ",expected
R8247 T11883 T11864 nsubj we,expected
R8248 T11884 T11864 aux would,expected
R8249 T11885 T11864 aux have,expected
R8250 T11886 T11887 aux to,find
R8251 T11887 T11864 xcomp find,expected
R8252 T11888 T11889 advmod less,amyloid
R8253 T11889 T11887 dobj amyloid,find
R8254 T11890 T11887 prep in,find
R8255 T11891 T11892 det the,animals
R8256 T11892 T11890 pobj animals,in
R8257 T11893 T11894 npadvmod dox,treated
R8258 T11894 T11892 amod treated,animals
R8259 T11895 T11894 punct -,treated
R8260 T11896 T11864 punct .,expected
R8261 T11898 T11899 advmod Clearly,was
R8262 T11900 T11899 punct ", ",was
R8263 T11901 T11899 nsubj that,was
R8264 T11902 T11899 neg not,was
R8265 T11903 T11904 det the,case
R8266 T11904 T11899 attr case,was
R8267 T11905 T11899 punct .,was
R8268 T11907 T11908 mark While,is
R8269 T11908 T11910 advcl is,demonstrate
R8270 T11909 T11908 nsubj it,is
R8271 T11911 T11908 acomp possible,is
R8272 T11912 T11913 mark that,acts
R8273 T11913 T11908 ccomp acts,is
R8274 T11914 T11913 nsubj dox,acts
R8275 T11915 T11913 prep in,acts
R8276 T11916 T11917 det some,way
R8277 T11917 T11915 pobj way,in
R8278 T11918 T11917 amod other,way
R8279 T11919 T11920 aux to,slow
R8280 T11920 T11913 advcl slow,acts
R8281 T11921 T11922 compound amyloid,clearance
R8282 T11922 T11920 dobj clearance,slow
R8283 T11923 T11910 punct ", ",demonstrate
R8284 T11924 T11910 nsubj data,demonstrate
R8285 T11925 T11924 prep from,data
R8286 T11926 T11927 amod multiple,studies
R8287 T11927 T11925 pobj studies,from
R8288 T11928 T11929 mark that,are
R8289 T11929 T11910 ccomp are,demonstrate
R8290 T11930 T11931 amod microglial,responses
R8291 T11931 T11929 nsubj responses,are
R8292 T11932 T11929 advmod normally,are
R8293 T11933 T11929 acomp weak,are
R8294 T11934 T11929 prep in,are
R8295 T11935 T11936 det the,models
R8296 T11936 T11934 pobj models,in
R8297 T11937 T11936 compound mouse,models
R8298 T11938 T11936 compound AD,models
R8299 T11939 T11940 punct [,37
R8300 T11940 T11929 parataxis 37,are
R8301 T11941 T11942 punct –,40
R8302 T11942 T11940 prep 40,37
R8303 T11943 T11940 punct ],37
R8304 T11944 T11929 punct ", ",are
R8305 T11945 T11929 cc and,are
R8306 T11946 T11947 advmod thus,is
R8307 T11947 T11929 conj is,are
R8308 T11948 T11947 nsubj it,is
R8309 T11949 T11947 acomp doubtful,is
R8310 T11950 T11951 mark that,affected
R8311 T11951 T11947 ccomp affected,is
R8312 T11952 T11953 npadvmod dox,mediated
R8313 T11953 T11955 amod mediated,inhibition
R8314 T11954 T11953 punct -,mediated
R8315 T11955 T11951 nsubj inhibition,affected
R8316 T11956 T11955 amod microglial,inhibition
R8317 T11957 T11958 det the,outcome
R8318 T11958 T11951 dobj outcome,affected
R8319 T11959 T11958 prep of,outcome
R8320 T11960 T11961 poss our,study
R8321 T11961 T11959 pobj study,of
R8322 T11962 T11910 punct .,demonstrate
R8323 T11964 T11965 det The,persistence
R8324 T11965 T11966 nsubj persistence,is
R8325 T11967 T11965 cc and,persistence
R8326 T11968 T11965 conj stability,persistence
R8327 T11969 T11965 prep of,persistence
R8328 T11970 T11971 compound amyloid,deposits
R8329 T11971 T11969 pobj deposits,of
R8330 T11972 T11965 prep in,persistence
R8331 T11973 T11974 poss our,system
R8332 T11974 T11972 pobj system,in
R8333 T11975 T11966 acomp unexpected,is
R8334 T11976 T11966 prep given,is
R8335 T11977 T11978 det the,speed
R8336 T11978 T11976 pobj speed,given
R8337 T11979 T11980 prep with,cleared
R8338 T11980 T11978 relcl cleared,speed
R8339 T11981 T11979 pobj which,with
R8340 T11982 T11983 compound Aβ,aggregates
R8341 T11983 T11980 nsubjpass aggregates,cleared
R8342 T11984 T11980 auxpass are,cleared
R8343 T11985 T11980 prep in,cleared
R8344 T11986 T11987 amod other,models
R8345 T11987 T11985 pobj models,in
R8346 T11988 T11987 compound mouse,models
R8347 T11989 T11987 prep of,models
R8348 T11990 T11991 amod therapeutic,intervention
R8349 T11991 T11989 pobj intervention,of
R8350 T11992 T11966 punct .,is
R8351 T11994 T11995 amod Anti-Aβ,antibodies
R8352 T11995 T11996 nsubjpass antibodies,shown
R8353 T11997 T11995 acl injected,antibodies
R8354 T11998 T11997 advmod directly,injected
R8355 T11999 T11997 prep into,injected
R8356 T12000 T12001 det the,brain
R8357 T12001 T11999 pobj brain,into
R8358 T12002 T11996 aux have,shown
R8359 T12003 T11996 auxpass been,shown
R8360 T12004 T12005 aux to,eliminate
R8361 T12005 T11996 xcomp eliminate,shown
R8362 T12006 T12007 compound amyloid,deposits
R8363 T12007 T12005 dobj deposits,eliminate
R8364 T12008 T12005 prep in,eliminate
R8365 T12009 T12010 advmod as,1
R8366 T12010 T12013 nummod 1,wk
R8367 T12011 T12010 amod little,1
R8368 T12012 T12010 quantmod as,1
R8369 T12013 T12008 pobj wk,in
R8370 T12014 T12013 prep after,wk
R8371 T12015 T12014 pobj treatment,after
R8372 T12016 T12017 punct [,49
R8373 T12017 T12005 parataxis 49,eliminate
R8374 T12018 T12019 punct –,51
R8375 T12019 T12017 prep 51,49
R8376 T12020 T12017 punct ],49
R8377 T12021 T11996 punct .,shown
R8378 T12023 T12024 amod Peripheral,injection
R8379 T12024 T12026 nsubj injection,decreases
R8380 T12025 T12024 compound antibody,injection
R8381 T12027 T12028 compound amyloid,load
R8382 T12028 T12026 dobj load,decreases
R8383 T12029 T12030 advmod more,broadly
R8384 T12030 T12026 advmod broadly,decreases
R8385 T12031 T12026 punct ", ",decreases
R8386 T12032 T12026 cc and,decreases
R8387 T12033 T12034 mark although,appear
R8388 T12034 T12038 advcl appear,reduce
R8389 T12035 T12034 nsubj it,appear
R8390 T12036 T12034 aux does,appear
R8391 T12037 T12034 neg not,appear
R8392 T12038 T12026 conj reduce,decreases
R8393 T12039 T12040 aux to,act
R8394 T12040 T12034 xcomp act,appear
R8395 T12041 T12042 advmod as,quickly
R8396 T12042 T12040 advmod quickly,act
R8397 T12043 T12042 prep as,quickly
R8398 T12044 T12045 amod local,injection
R8399 T12045 T12043 pobj injection,as
R8400 T12046 T12038 punct ", ",reduce
R8401 T12047 T12038 aux can,reduce
R8402 T12048 T12038 advmod significantly,reduce
R8403 T12086 T12084 pobj area,in
R8404 T12049 T12050 compound amyloid,load
R8405 T12087 T12086 prep of,area
R8406 T12050 T12038 dobj load,reduce
R8407 T12088 T12089 det the,site
R8408 T12051 T12038 prep within,reduce
R8409 T12052 T12053 nummod 2,mo
R8410 T12089 T12087 pobj site,of
R8411 T12090 T12089 compound injection,site
R8412 T12053 T12051 pobj mo,within
R8413 T12091 T12092 punct [,54
R8414 T12092 T12073 parataxis 54,reduce
R8415 T12054 T12053 prep of,mo
R8416 T12093 T12092 punct ],54
R8417 T12094 T12066 punct .,shown
R8418 T12055 T12056 amod initial,treatment
R8419 T12096 T12097 amod Careful,study
R8420 T12097 T12098 nsubj study,suggested
R8421 T12056 T12054 pobj treatment,of
R8422 T12099 T12097 prep of,study
R8423 T12057 T12058 punct [,53
R8424 T12100 T12101 det the,mechanism
R8425 T12101 T12099 pobj mechanism,of
R8426 T12058 T12038 parataxis 53,reduce
R8427 T12102 T12101 prep behind,mechanism
R8428 T12103 T12102 pobj several,behind
R8429 T12104 T12103 prep of,several
R8430 T12059 T12058 nummod 52,53
R8431 T12105 T12106 det the,therapies
R8432 T12106 T12104 pobj therapies,of
R8433 T12107 T12108 npadvmod antibody,mediated
R8434 T12108 T12106 amod mediated,therapies
R8435 T12109 T12108 punct -,mediated
R8436 T12060 T12058 punct ",",53
R8437 T12110 T12098 aux has,suggested
R8438 T12111 T12112 mark that,play
R8439 T12112 T12098 ccomp play,suggested
R8440 T12061 T12058 punct ],53
R8441 T12113 T12114 amod activated,microglia
R8442 T12114 T12112 nsubj microglia,play
R8443 T12115 T12116 det an,role
R8444 T12062 T12026 punct .,decreases
R8445 T12116 T12112 dobj role,play
R8446 T12117 T12116 amod important,role
R8447 T12064 T12065 advmod More,recently
R8448 T12118 T12112 prep in,play
R8449 T12119 T12120 det the,removal
R8450 T12120 T12118 pobj removal,in
R8451 T12121 T12120 prep of,removal
R8452 T12065 T12066 advmod recently,shown
R8453 T12122 T12123 amod fibrillar,plaques
R8454 T12123 T12121 pobj plaques,of
R8455 T12124 T12112 prep after,play
R8456 T12067 T12066 punct ", ",shown
R8457 T12125 T12124 pobj immunization,after
R8458 T12126 T12127 punct [,55
R8459 T12127 T12098 parataxis 55,suggested
R8460 T12128 T12127 nummod 50,55
R8461 T12068 T12069 det an,approach
R8462 T12129 T12127 punct ",",55
R8463 T12130 T12127 nummod 52,55
R8464 T12131 T12127 punct ",",55
R8465 T12069 T12066 nsubj approach,shown
R8466 T12132 T12127 punct ],55
R8467 T12133 T12098 punct .,suggested
R8468 T12070 T12069 amod alternative,approach
R8469 T12135 T12136 advmod However,noted
R8470 T12071 T12066 aux has,shown
R8471 T12137 T12136 punct ", ",noted
R8472 T12138 T12136 nsubjpass it,noted
R8473 T12139 T12136 aux has,noted
R8474 T12072 T12073 mark that,reduce
R8475 T12140 T12136 auxpass been,noted
R8476 T12141 T12142 mark that,has
R8477 T12073 T12066 ccomp reduce,shown
R8478 T12142 T12136 ccomp has,noted
R8479 T12143 T12142 nsubj deletion,has
R8480 T12144 T12143 prep of,deletion
R8481 T12074 T12075 amod lentiviral,transfer
R8482 T12145 T12146 det the,receptor
R8483 T12146 T12144 pobj receptor,of
R8484 T12147 T12146 compound Fc,receptor
R8485 T12148 T12146 punct (,receptor
R8486 T12149 T12150 det the,receptor
R8487 T12075 T12073 nsubj transfer,reduce
R8488 T12150 T12146 appos receptor,receptor
R8489 T12151 T12150 amod primary,receptor
R8490 T12152 T12150 prep for,receptor
R8491 T12076 T12075 prep of,transfer
R8492 T12153 T12154 amod microglial,opsinization
R8493 T12154 T12152 pobj opsinization,for
R8494 T12155 T12154 prep of,opsinization
R8495 T12077 T12076 pobj neprilysin,of
R8496 T12156 T12157 compound antibody,antigen
R8497 T12157 T12159 compound antigen,complexes
R8498 T12158 T12157 punct –,antigen
R8499 T12078 T12073 aux can,reduce
R8500 T12159 T12155 pobj complexes,of
R8501 T12160 T12143 punct ),deletion
R8502 T12079 T12073 advmod also,reduce
R8503 T12161 T12143 prep in,deletion
R8504 T12162 T12163 npadvmod APP,transgenic
R8505 T12163 T12164 amod transgenic,models
R8506 T12080 T12081 det the,number
R8507 T12164 T12161 pobj models,in
R8508 T12165 T12164 compound mouse,models
R8509 T12166 T12167 det no,impact
R8510 T12081 T12073 dobj number,reduce
R8511 T12167 T12142 dobj impact,has
R8512 T12168 T12167 prep on,impact
R8513 T12082 T12081 prep of,number
R8514 T12169 T12170 det the,effectiveness
R8515 T12170 T12168 pobj effectiveness,on
R8516 T12171 T12170 prep of,effectiveness
R8517 T12083 T12082 pobj aggregates,of
R8518 T12172 T12173 npadvmod antibody,mediated
R8519 T12084 T12073 prep in,reduce
R8520 T12085 T12086 det the,area
R8521 T12173 T12175 amod mediated,therapy
R8522 T12192 T12191 prep of,lack
R8523 T12174 T12173 punct -,mediated
R8524 T12175 T12171 pobj therapy,of
R8525 T12176 T12177 punct [,57
R8526 T12177 T12142 parataxis 57,has
R8527 T12193 T12194 compound microglia,activation
R8528 T12178 T12177 nummod 56,57
R8529 T12179 T12177 punct ",",57
R8530 T12180 T12177 punct ],57
R8531 T12194 T12192 pobj activation,of
R8532 T12181 T12136 punct .,noted
R8533 T12195 T12196 det the,difference
R8534 T12183 T12184 nsubj It,is
R8535 T12196 T12190 attr difference,is
R8536 T12185 T12184 punct ", ",is
R8537 T12186 T12184 advmod nevertheless,is
R8538 T12187 T12184 punct ", ",is
R8539 T12188 T12184 acomp possible,is
R8540 T12189 T12190 mark that,is
R8541 T12190 T12184 ccomp is,is
R8542 T12197 T12196 amod major,difference
R8543 T12191 T12190 nsubj lack,is
R8544 T12198 T12196 prep between,difference
R8545 T12199 T12200 det the,clearance
R8546 T12200 T12198 pobj clearance,between
R8547 T12201 T12200 amod slow,clearance
R8548 T12202 T12200 acl described,clearance
R8549 T12203 T12202 advmod here,described
R8550 T12298 T12297 punct ],58
R8551 T12299 T12293 cc or,expression
R8552 T12204 T12200 punct ", ",clearance
R8553 T12300 T12301 amod central,injection
R8554 T12301 T12293 conj injection,expression
R8555 T12302 T12301 prep of,injection
R8556 T12205 T12206 advmod where,expected
R8557 T12303 T12302 pobj lipopolysaccharide,of
R8558 T12304 T12305 punct [,60
R8559 T12305 T12303 parataxis 60,lipopolysaccharide
R8560 T12206 T12200 relcl expected,clearance
R8561 T12306 T12305 nummod 59,60
R8562 T12307 T12305 punct ",",60
R8563 T12207 T12208 det no,perturbation
R8564 T12308 T12305 punct ],60
R8565 T12309 T12282 aux can,reduce
R8566 T12310 T12282 prep by,reduce
R8567 T12208 T12206 nsubjpass perturbation,expected
R8568 T12311 T12310 pobj itself,by
R8569 T12312 T12282 advmod substantially,reduce
R8570 T12209 T12208 prep of,perturbation
R8571 T12313 T12314 compound plaque,burden
R8572 T12314 T12282 dobj burden,reduce
R8573 T12315 T12282 prep in,reduce
R8574 T12210 T12211 det the,system
R8575 T12316 T12317 npadvmod APP,transgenic
R8576 T12317 T12318 amod transgenic,mice
R8577 T12211 T12209 pobj system,of
R8578 T12318 T12315 pobj mice,in
R8579 T12319 T12282 punct .,reduce
R8580 T12212 T12211 amod immune,system
R8581 T12321 T12322 cc But,reaggregates
R8582 T12213 T12206 auxpass is,expected
R8583 T12323 T12322 prep in,reaggregates
R8584 T12324 T12325 det the,case
R8585 T12325 T12323 pobj case,in
R8586 T12214 T12200 punct ", ",clearance
R8587 T12326 T12325 prep of,case
R8588 T12327 T12328 amod acute,activation
R8589 T12328 T12326 pobj activation,of
R8590 T12329 T12330 npadvmod antibody,mediated
R8591 T12330 T12328 amod mediated,activation
R8592 T12215 T12200 cc and,clearance
R8593 T12331 T12329 punct -,antibody
R8594 T12332 T12329 cc and,antibody
R8595 T12333 T12332 punct /,and
R8596 T12216 T12217 det the,clearance
R8597 T12334 T12332 cc or,and
R8598 T12335 T12329 conj injury,antibody
R8599 T12336 T12330 punct -,mediated
R8600 T12217 T12200 conj clearance,clearance
R8601 T12337 T12322 punct ", ",reaggregates
R8602 T12338 T12339 mark once,passed
R8603 T12339 T12322 advcl passed,reaggregates
R8604 T12218 T12217 amod rapid,clearance
R8605 T12340 T12341 det the,inflammation
R8606 T12341 T12339 nsubj inflammation,passed
R8607 T12219 T12217 acl described,clearance
R8608 T12342 T12339 aux has,passed
R8609 T12220 T12219 prep in,described
R8610 T12343 T12339 punct ", ",passed
R8611 T12221 T12220 pobj studies,in
R8612 T12344 T12339 cc and,passed
R8613 T12345 T12346 det the,antibody
R8614 T12346 T12347 nsubjpass antibody,cleared
R8615 T12222 T12221 acl involving,studies
R8616 T12347 T12339 conj cleared,passed
R8617 T12223 T12224 nmod antibody,injection
R8618 T12348 T12346 cc and,antibody
R8619 T12349 T12350 amod bound,peptide
R8620 T12350 T12346 conj peptide,antibody
R8621 T12224 T12222 dobj injection,involving
R8622 T12351 T12347 aux have,cleared
R8623 T12352 T12347 auxpass been,cleared
R8624 T12353 T12347 cc and,cleared
R8625 T12225 T12223 cc or,antibody
R8626 T12354 T12347 conj degraded,cleared
R8627 T12355 T12322 punct ", ",reaggregates
R8628 T12356 T12357 det the,Aβ
R8629 T12226 T12223 conj viral,antibody
R8630 T12357 T12322 nsubj Aβ,reaggregates
R8631 T12358 T12357 amod remaining,Aβ
R8632 T12227 T12184 punct .,is
R8633 T12359 T12322 advmod quickly,reaggregates
R8634 T12360 T12322 cc and,reaggregates
R8635 T12361 T12362 compound amyloid,pathology
R8636 T12229 T12230 prep In,be
R8637 T12362 T12363 nsubjpass pathology,reestablished
R8638 T12363 T12322 conj reestablished,reaggregates
R8639 T12364 T12363 auxpass is,reestablished
R8640 T12365 T12366 punct [,49
R8641 T12366 T12363 parataxis 49,reestablished
R8642 T12367 T12366 punct ],49
R8643 T12368 T12322 punct .,reaggregates
R8644 T12231 T12229 pobj isolation,In
R8645 T12370 T12371 det This,finding
R8646 T12371 T12372 nsubj finding,reinforces
R8647 T12232 T12230 punct ", ",be
R8648 T12373 T12374 det the,notion
R8649 T12374 T12372 dobj notion,reinforces
R8650 T12375 T12376 mark that,maintain
R8651 T12233 T12234 amod mild,activation
R8652 T12376 T12374 acl maintain,notion
R8653 T12377 T12376 prep without,maintain
R8654 T12234 T12230 nsubj activation,be
R8655 T12378 T12379 amod continued,stimulation
R8656 T12379 T12377 pobj stimulation,without
R8657 T12380 T12376 punct ", ",maintain
R8658 T12235 T12234 prep of,activation
R8659 T12381 T12376 nsubj microglia,maintain
R8660 T12382 T12381 prep in,microglia
R8661 T12236 T12235 pobj microglia,of
R8662 T12383 T12384 compound mouse,models
R8663 T12384 T12382 pobj models,in
R8664 T12385 T12376 aux do,maintain
R8665 T12237 T12234 prep by,activation
R8666 T12386 T12376 neg not,maintain
R8667 T12387 T12388 det the,level
R8668 T12388 T12376 dobj level,maintain
R8669 T12238 T12239 compound injection,damage
R8670 T12389 T12388 amod same,level
R8671 T12390 T12388 prep of,level
R8672 T12239 T12237 pobj damage,by
R8673 T12391 T12392 amod sustained,activation
R8674 T12392 T12390 pobj activation,of
R8675 T12393 T12394 dep that,occur
R8676 T12240 T12239 cc or,damage
R8677 T12394 T12388 relcl occur,level
R8678 T12395 T12394 aux may,occur
R8679 T12241 T12239 conj opsinization,damage
R8680 T12396 T12394 prep in,occur
R8681 T12397 T12396 pobj humans,in
R8682 T12398 T12372 punct .,reinforces
R8683 T12242 T12230 aux may,be
R8684 T12400 T12401 nsubj SantaCruz,published
R8685 T12243 T12230 neg not,be
R8686 T12402 T12403 advmod et,al.
R8687 T12403 T12400 advmod al.,SantaCruz
R8688 T12244 T12230 acomp adequate,be
R8689 T12245 T12246 aux to,induce
R8690 T12246 T12230 advcl induce,be
R8691 T12404 T12401 advmod recently,published
R8692 T12247 T12248 amod substantial,phagocytosis
R8693 T12405 T12406 det a,study
R8694 T12406 T12401 dobj study,published
R8695 T12407 T12406 prep of,study
R8696 T12408 T12407 pobj mice,of
R8697 T12409 T12410 dep that,express
R8698 T12410 T12408 relcl express,mice
R8699 T12248 T12246 dobj phagocytosis,induce
R8700 T12411 T12412 nmod P301L,tau
R8701 T12412 T12410 dobj tau,express
R8702 T12249 T12230 punct ", ",be
R8703 T12413 T12412 amod human,tau
R8704 T12414 T12410 prep via,express
R8705 T12415 T12416 det a,system
R8706 T12250 T12230 cc but,be
R8707 T12416 T12414 pobj system,via
R8708 T12417 T12416 amod similar,system
R8709 T12251 T12252 advmod when,combined
R8710 T12418 T12416 compound vector,system
R8711 T12419 T12420 punct [,61
R8712 T12420 T12401 parataxis 61,published
R8713 T12252 T12253 advcl combined,work
R8714 T12421 T12420 punct ],61
R8715 T12422 T12401 punct .,published
R8716 T12253 T12230 conj work,be
R8717 T12424 T12425 prep As,found
R8718 T12254 T12252 prep with,combined
R8719 T12426 T12424 prep in,As
R8720 T12427 T12428 poss our,mice
R8721 T12255 T12256 det an,agent
R8722 T12256 T12254 pobj agent,with
R8723 T12428 T12426 pobj mice,in
R8724 T12429 T12430 compound tet,off
R8725 T12257 T12258 npadvmod Aβ,lowering
R8726 T12430 T12428 compound off,mice
R8727 T12431 T12430 punct -,off
R8728 T12258 T12256 amod lowering,agent
R8729 T12432 T12428 compound APP,mice
R8730 T12433 T12425 punct ", ",found
R8731 T12434 T12425 nsubj SantaCruz,found
R8732 T12259 T12258 punct -,lowering
R8733 T12435 T12436 advmod et,al.
R8734 T12436 T12434 advmod al.,SantaCruz
R8735 T12437 T12438 mark that,cleared
R8736 T12260 T12256 punct ", ",agent
R8737 T12438 T12425 ccomp cleared,found
R8738 T12439 T12440 nmod tau,tangles
R8739 T12261 T12262 amod such,as
R8740 T12440 T12438 nsubjpass tangles,cleared
R8741 T12441 T12440 amod neurofibrillary,tangles
R8742 T12262 T12256 prep as,agent
R8743 T12442 T12440 punct ", ",tangles
R8744 T12443 T12440 prep like,tangles
R8745 T12444 T12445 compound amyloid,plaques
R8746 T12445 T12443 pobj plaques,like
R8747 T12446 T12438 punct ", ",cleared
R8748 T12263 T12264 npadvmod neprilysin,targeted
R8749 T12447 T12438 auxpass are,cleared
R8750 T12448 T12438 neg not,cleared
R8751 T12449 T12438 advmod efficiently,cleared
R8752 T12450 T12438 prep following,cleared
R8753 T12264 T12268 amod targeted,antibodies
R8754 T12451 T12452 compound transgene,suppression
R8755 T12452 T12450 pobj suppression,following
R8756 T12453 T12425 punct .,found
R8757 T12265 T12263 cc or,neprilysin
R8758 T12455 T12456 det The,lack
R8759 T12456 T12457 nsubj lack,comes
R8760 T12266 T12263 conj Aβ,neprilysin
R8761 T12458 T12456 prep of,lack
R8762 T12267 T12264 punct -,targeted
R8763 T12459 T12458 pobj clearance,of
R8764 T12460 T12456 prep in,lack
R8765 T12461 T12462 det both,models
R8766 T12268 T12262 pobj antibodies,as
R8767 T12462 T12460 pobj models,in
R8768 T12463 T12462 prep of,models
R8769 T12269 T12253 punct ", ",work
R8770 T12464 T12465 compound AD,pathology
R8771 T12465 T12463 pobj pathology,of
R8772 T12466 T12457 prep as,comes
R8773 T12270 T12271 det the,two
R8774 T12467 T12468 det a,contrast
R8775 T12468 T12466 pobj contrast,as
R8776 T12271 T12253 nsubj two,work
R8777 T12469 T12468 amod stark,contrast
R8778 T12470 T12468 prep to,contrast
R8779 T12471 T12472 det the,removal
R8780 T12272 T12253 aux may,work
R8781 T12472 T12470 pobj removal,to
R8782 T12473 T12472 amod rapid,removal
R8783 T12273 T12253 prep in,work
R8784 T12474 T12472 prep of,removal
R8785 T12475 T12476 compound protein,aggregates
R8786 T12476 T12474 pobj aggregates,of
R8787 T12274 T12273 pobj concert,in
R8788 T12477 T12472 acl found,removal
R8789 T12478 T12477 prep in,found
R8790 T12479 T12480 amod similar,models
R8791 T12275 T12276 aux to,clear
R8792 T12480 T12478 pobj models,in
R8793 T12481 T12482 compound tet,off
R8794 T12276 T12253 advcl clear,work
R8795 T12482 T12480 compound off,models
R8796 T12483 T12482 punct -,off
R8797 T12484 T12480 compound mouse,models
R8798 T12485 T12480 prep of,models
R8799 T12486 T12487 nmod Huntington,disease
R8800 T12487 T12485 pobj disease,of
R8801 T12277 T12278 compound peptide,deposits
R8802 T12488 T12489 punct [,32
R8803 T12489 T12486 parataxis 32,Huntington
R8804 T12490 T12489 punct ],32
R8805 T12278 T12276 dobj deposits,clear
R8806 T12491 T12486 cc and,Huntington
R8807 T12492 T12486 conj prion,Huntington
R8808 T12493 T12494 punct [,62
R8809 T12279 T12253 punct .,work
R8810 T12494 T12487 parataxis 62,disease
R8811 T12495 T12494 punct ],62
R8812 T12281 T12282 advcl Consistent,reduce
R8813 T12496 T12457 punct .,comes
R8814 T12498 T12499 prep In,led
R8815 T12283 T12281 prep with,Consistent
R8816 T12500 T12501 det these,cases
R8817 T12501 T12498 pobj cases,In
R8818 T12502 T12499 punct ", ",led
R8819 T12503 T12499 csubj disrupting,led
R8820 T12284 T12285 det this,hypothesis
R8821 T12504 T12505 det the,input
R8822 T12505 T12503 dobj input,disrupting
R8823 T12506 T12505 prep of,input
R8824 T12285 T12283 pobj hypothesis,with
R8825 T12507 T12508 amod new,monomer
R8826 T12508 T12506 pobj monomer,of
R8827 T12509 T12505 prep to,input
R8828 T12286 T12282 punct ", ",reduce
R8829 T12287 T12288 amod strong,activation
R8830 T12288 T12282 nsubj activation,reduce
R8831 T12289 T12288 prep of,activation
R8832 T12510 T12511 det the,system
R8833 T12290 T12289 pobj microglia,of
R8834 T12511 T12509 pobj system,to
R8835 T12512 T12503 prep via,disrupting
R8836 T12513 T12514 npadvmod dox,mediated
R8837 T12291 T12288 prep through,activation
R8838 T12292 T12293 amod transgenic,expression
R8839 T12514 T12516 amod mediated,suppression
R8840 T12293 T12291 pobj expression,through
R8841 T12515 T12514 punct -,mediated
R8842 T12516 T12512 pobj suppression,via
R8843 T12517 T12516 compound transgene,suppression
R8844 T12294 T12293 prep of,expression
R8845 T12518 T12499 prep to,led
R8846 T12519 T12520 advmod relatively,rapid
R8847 T12295 T12294 pobj TGFβ,of
R8848 T12520 T12521 amod rapid,clearance
R8849 T12521 T12518 pobj clearance,to
R8850 T12522 T12521 prep of,clearance
R8851 T12523 T12524 compound protein,aggregates
R8852 T12296 T12297 punct [,58
R8853 T12524 T12522 pobj aggregates,of
R8854 T12525 T12499 punct .,led
R8855 T12297 T12295 parataxis 58,TGFβ
R8856 T12527 T12528 prep By,suggest
R8857 T12529 T12527 pobj contrast,By
R8858 T12616 T12615 punct -,off
R8859 T12530 T12528 punct ", ",suggest
R8860 T12531 T12532 poss our,study
R8861 T12532 T12528 nsubj study,suggest
R8862 T12617 T12613 compound tau,mice
R8863 T12533 T12532 cc and,study
R8864 T12534 T12532 conj that,study
R8865 T12535 T12534 prep of,that
R8866 T12618 T12619 mark that,required
R8867 T12536 T12535 pobj SantaCruz,of
R8868 T12537 T12538 advmod et,al.
R8869 T12538 T12536 advmod al.,SantaCruz
R8870 T12619 T12610 ccomp required,suggest
R8871 T12539 T12540 mark that,be
R8872 T12540 T12528 ccomp be,suggest
R8873 T12541 T12542 compound protein,aggregates
R8874 T12620 T12621 compound protein,clearance
R8875 T12542 T12540 nsubj aggregates,be
R8876 T12543 T12542 prep in,aggregates
R8877 T12621 T12619 nsubjpass clearance,required
R8878 T12544 T12543 pobj AD,in
R8879 T12545 T12540 aux may,be
R8880 T12546 T12547 advmod more,tenacious
R8881 T12622 T12619 aux may,required
R8882 T12547 T12540 acomp tenacious,be
R8883 T12548 T12547 prep than,tenacious
R8884 T12549 T12548 prep in,than
R8885 T12623 T12619 prep in,required
R8886 T12550 T12551 amod other,disorders
R8887 T12551 T12549 pobj disorders,in
R8888 T12624 T12623 pobj fact,in
R8889 T12552 T12551 amod neurodegenerative,disorders
R8890 T12553 T12528 punct .,suggest
R8891 T12625 T12619 neg not,required
R8892 T12555 T12556 advmod Perhaps,are
R8893 T12626 T12619 auxpass be,required
R8894 T12557 T12558 mark once,aggregated
R8895 T12558 T12556 advcl aggregated,are
R8896 T12627 T12619 prep for,required
R8897 T12559 T12556 punct ", ",are
R8898 T12560 T12556 nsubj Aβ,are
R8899 T12561 T12560 cc and,Aβ
R8900 T12628 T12629 amod cognitive,improvement
R8901 T12562 T12560 conj tau,Aβ
R8902 T12563 T12564 advmod either,stable
R8903 T12564 T12556 acomp stable,are
R8904 T12565 T12564 advmod inherently,stable
R8905 T12566 T12564 advmod more,stable
R8906 T12629 T12627 pobj improvement,for
R8907 T12567 T12564 prep than,stable
R8908 T12568 T12569 amod other,aggregates
R8909 T12569 T12567 pobj aggregates,than
R8910 T12630 T12619 prep following,required
R8911 T12570 T12569 compound protein,aggregates
R8912 T12571 T12564 cc or,stable
R8913 T12572 T12573 advmod more,resistant
R8914 T12631 T12632 compound transgene,suppression
R8915 T12573 T12564 conj resistant,stable
R8916 T12574 T12573 prep to,resistant
R8917 T12575 T12576 advmod intra,extracellular
R8918 T12632 T12630 pobj suppression,following
R8919 T12576 T12579 amod extracellular,mechanisms
R8920 T12577 T12576 punct -,extracellular
R8921 T12633 T12634 punct [,61
R8922 T12578 T12576 cc and,extracellular
R8923 T12579 T12574 pobj mechanisms,to
R8924 T12580 T12579 compound clearance,mechanisms
R8925 T12634 T12619 parataxis 61,required
R8926 T12581 T12556 punct .,are
R8927 T12635 T12634 punct ],61
R8928 T12583 T12584 nummod One,question
R8929 T12584 T12585 nsubj question,is
R8930 T12636 T12610 punct .,suggest
R8931 T12586 T12587 nsubj we,were
R8932 T12587 T12584 advcl were,question
R8933 T12638 T12639 prep At,is
R8934 T12588 T12587 neg not,were
R8935 T12589 T12587 acomp able,were
R8936 T12590 T12591 aux to,address
R8937 T12591 T12589 xcomp address,able
R8938 T12640 T12638 amod present,At
R8939 T12592 T12591 prep in,address
R8940 T12593 T12594 det this,study
R8941 T12594 T12592 pobj study,in
R8942 T12595 T12596 mark whether,halts
R8943 T12641 T12639 punct ", ",is
R8944 T12596 T12585 ccomp halts,is
R8945 T12597 T12596 csubj abrogating,halts
R8946 T12642 T12639 prep because,is
R8947 T12598 T12597 dobj synthesis,abrogating
R8948 T12599 T12598 prep of,synthesis
R8949 T12643 T12642 pcomp of,because
R8950 T12600 T12601 amod new,Aβ
R8951 T12601 T12599 pobj Aβ,of
R8952 T12644 T12645 amod unexpected,abnormalities
R8953 T12602 T12603 det the,progression
R8954 T12603 T12596 dobj progression,halts
R8955 T12604 T12603 prep of,progression
R8956 T12645 T12642 pobj abnormalities,because
R8957 T12605 T12606 amod cognitive,decline
R8958 T12606 T12604 pobj decline,of
R8959 T12607 T12585 punct .,is
R8960 T12646 T12645 amod noncognitive,abnormalities
R8961 T12609 T12610 nsubj Studies,suggest
R8962 T12647 T12645 amod behavioral,abnormalities
R8963 T12611 T12609 prep from,Studies
R8964 T12612 T12613 det the,mice
R8965 T12648 T12639 punct ", ",is
R8966 T12613 T12611 pobj mice,from
R8967 T12614 T12615 compound tet,off
R8968 T12649 T12639 nsubj it,is
R8969 T12615 T12613 compound off,mice
R8970 T12650 T12639 neg not,is
R8971 T12651 T12639 acomp clear,is
R8972 T12652 T12653 mark whether,used
R8973 T12653 T12639 ccomp used,is
R8974 T12722 T12723 advmod when,tested
R8975 T12654 T12655 det the,mice
R8976 T12723 T12705 advcl tested,showed
R8977 T12724 T12723 prep in,tested
R8978 T12655 T12653 nsubjpass mice,used
R8979 T12725 T12726 det the,maze
R8980 T12726 T12724 pobj maze,in
R8981 T12656 T12657 compound tet,off
R8982 T12727 T12726 compound Morris,maze
R8983 T12728 T12726 compound water,maze
R8984 T12729 T12705 punct .,showed
R8985 T12657 T12655 compound off,mice
R8986 T12731 T12732 nsubj Expression,makes
R8987 T12658 T12657 punct -,off
R8988 T12733 T12731 prep of,Expression
R8989 T12734 T12735 det this,phenotype
R8990 T12659 T12655 compound APP,mice
R8991 T12735 T12733 pobj phenotype,of
R8992 T12736 T12737 amod standard,tests
R8993 T12737 T12738 nsubj tests,uninterpretable
R8994 T12660 T12653 aux can,used
R8995 T12738 T12732 ccomp uninterpretable,makes
R8996 T12739 T12737 prep of,tests
R8997 T12740 T12739 pobj learning,of
R8998 T12661 T12653 auxpass be,used
R8999 T12741 T12740 cc and,learning
R9000 T12742 T12740 conj memory,learning
R9001 T12662 T12663 aux to,address
R9002 T12743 T12732 punct .,makes
R9003 T12745 T12746 nsubj Hyperactivity,inhibits
R9004 T12663 T12653 advcl address,used
R9005 T12747 T12746 advmod nonspecifically,inhibits
R9006 T12748 T12749 npadvmod choice,driven
R9007 T12749 T12751 amod driven,changes
R9008 T12664 T12665 det the,question
R9009 T12750 T12749 punct -,driven
R9010 T12751 T12746 dobj changes,inhibits
R9011 T12665 T12663 dobj question,address
R9012 T12752 T12751 prep in,changes
R9013 T12753 T12752 pobj movement,in
R9014 T12666 T12665 amod same,question
R9015 T12754 T12751 punct ", ",changes
R9016 T12755 T12756 det the,element
R9017 T12756 T12751 appos element,changes
R9018 T12667 T12663 prep in,address
R9019 T12757 T12756 amod key,element
R9020 T12758 T12756 prep behind,element
R9021 T12759 T12760 det all,paradigms
R9022 T12668 T12669 det the,context
R9023 T12760 T12758 pobj paradigms,behind
R9024 T12761 T12760 amod cognitive,paradigms
R9025 T12669 T12667 pobj context,in
R9026 T12762 T12760 amod behavioral,paradigms
R9027 T12763 T12746 punct .,inhibits
R9028 T12670 T12669 prep of,context
R9029 T12765 T12766 nsubj We,working
R9030 T12671 T12672 compound amyloid,pathology
R9031 T12767 T12766 aux are,working
R9032 T12768 T12766 advmod currently,working
R9033 T12769 T12770 aux to,determine
R9034 T12672 T12670 pobj pathology,of
R9035 T12770 T12766 xcomp determine,working
R9036 T12771 T12772 mark whether,correlates
R9037 T12772 T12770 ccomp correlates,determine
R9038 T12673 T12639 punct .,is
R9039 T12773 T12772 nsubj hyperactivity,correlates
R9040 T12774 T12772 prep with,correlates
R9041 T12675 T12676 det Both,lines
R9042 T12775 T12774 pobj expression,with
R9043 T12776 T12775 prep of,expression
R9044 T12777 T12778 det the,holoprotein
R9045 T12676 T12677 nsubj lines,display
R9046 T12678 T12676 prep of,lines
R9047 T12778 T12776 pobj holoprotein,of
R9048 T12779 T12780 compound APPswe,ind
R9049 T12780 T12778 compound ind,holoprotein
R9050 T12781 T12780 punct /,ind
R9051 T12679 T12680 compound tTA,APP
R9052 T12782 T12775 cc or,expression
R9053 T12783 T12784 poss its,derivatives
R9054 T12784 T12775 conj derivatives,expression
R9055 T12680 T12682 compound APP,mice
R9056 T12785 T12784 amod proteolytic,derivatives
R9057 T12786 T12766 punct .,working
R9058 T12788 T12789 amod Preliminary,studies
R9059 T12681 T12680 punct /,APP
R9060 T12789 T12790 nsubj studies,suggest
R9061 T12791 T12792 mark that,appear
R9062 T12682 T12678 pobj mice,of
R9063 T12792 T12790 ccomp appear,suggest
R9064 T12793 T12792 nsubj hyperactivity,appear
R9065 T12683 T12684 nsubj we,studied
R9066 T12794 T12792 aux does,appear
R9067 T12795 T12792 neg not,appear
R9068 T12684 T12676 advcl studied,lines
R9069 T12796 T12792 advmod quickly,appear
R9070 T12797 T12798 advmod when,shifted
R9071 T12798 T12792 advcl shifted,appear
R9072 T12685 T12684 advmod here,studied
R9073 T12799 T12800 npadvmod dox,reared
R9074 T12800 T12802 amod reared,mice
R9075 T12801 T12800 punct -,reared
R9076 T12686 T12687 amod extreme,hyperactivity
R9077 T12802 T12798 nsubjpass mice,shifted
R9078 T12803 T12798 auxpass are,shifted
R9079 T12687 T12677 dobj hyperactivity,display
R9080 T12804 T12798 prep to,shifted
R9081 T12805 T12806 amod nonmedicated,diets
R9082 T12806 T12804 pobj diets,to
R9083 T12688 T12687 amod visible,hyperactivity
R9084 T12807 T12808 punct (,data
R9085 T12808 T12798 parataxis data,shifted
R9086 T12809 T12810 compound J.,J.
R9087 T12689 T12688 prep as,visible
R9088 T12810 T12808 dep J.,data
R9089 T12811 T12810 compound L.,J.
R9090 T12812 T12808 punct ", ",data
R9091 T12690 T12691 compound cage,circling
R9092 T12813 T12808 amod unpublished,data
R9093 T12814 T12808 punct ),data
R9094 T12815 T12790 punct .,suggest
R9095 T12691 T12689 pobj circling,as
R9096 T12817 T12818 det These,data
R9097 T12692 T12688 cc and,visible
R9098 T12818 T12819 nsubj data,indicate
R9099 T12820 T12819 aux may,indicate
R9100 T12693 T12688 conj quantified,visible
R9101 T12821 T12822 mark that,is
R9102 T12822 T12819 ccomp is,indicate
R9103 T12694 T12693 agent by,quantified
R9104 T12823 T12824 det the,culprit
R9105 T12824 T12822 nsubj culprit,is
R9106 T12825 T12824 amod neuroactive,culprit
R9107 T12695 T12696 compound activity,monitoring
R9108 T12826 T12827 neg not,immediately
R9109 T12827 T12822 advmod immediately,is
R9110 T12696 T12694 pobj monitoring,by
R9111 T12697 T12698 punct (,see
R9112 T12828 T12822 acomp present,is
R9113 T12698 T12677 parataxis see,display
R9114 T12829 T12830 mark after,initiated
R9115 T12830 T12822 advcl initiated,is
R9116 T12831 T12832 amod transgenic,synthesis
R9117 T12699 T12698 dobj Figure,see
R9118 T12832 T12830 nsubjpass synthesis,initiated
R9119 T12700 T12699 nummod 7,Figure
R9120 T12833 T12832 compound APP,synthesis
R9121 T12834 T12830 auxpass is,initiated
R9122 T12835 T12822 punct ", ",is
R9123 T12701 T12698 punct ),see
R9124 T12836 T12822 cc but,is
R9125 T12837 T12822 conj requires,is
R9126 T12702 T12677 punct .,display
R9127 T12838 T12839 amod additional,time
R9128 T12839 T12837 dobj time,requires
R9129 T12704 T12705 nsubj Many,showed
R9130 T12840 T12841 aux to,develop
R9131 T12841 T12839 advcl develop,time
R9132 T12842 T12819 punct .,indicate
R9133 T12706 T12704 prep of,Many
R9134 T12844 T12845 advmod Alternatively,caused
R9135 T12707 T12708 det the,mice
R9136 T12846 T12845 punct ", ",caused
R9137 T12847 T12845 nsubjpass hyperactivity,caused
R9138 T12708 T12706 pobj mice,of
R9139 T12848 T12845 aux may,caused
R9140 T12849 T12845 auxpass be,caused
R9141 T12850 T12845 agent by,caused
R9142 T12709 T12710 amod double,transgenic
R9143 T12851 T12852 amod neuronal,alterations
R9144 T12852 T12850 pobj alterations,by
R9145 T12853 T12845 prep due,caused
R9146 T12710 T12708 amod transgenic,mice
R9147 T12854 T12853 pcomp to,due
R9148 T12855 T12856 compound transgene,expression
R9149 T12711 T12712 amod similar,patterns
R9150 T12856 T12853 pobj expression,due
R9151 T12857 T12856 prep during,expression
R9152 T12858 T12859 amod early,postnatal
R9153 T12712 T12705 dobj patterns,showed
R9154 T12859 T12860 amod postnatal,development
R9155 T12860 T12857 pobj development,during
R9156 T12861 T12845 punct .,caused
R9157 T12713 T12712 amod circular,patterns
R9158 T12863 T12864 amod Further,experiments
R9159 T12714 T12712 prep of,patterns
R9160 T12864 T12865 nsubjpass experiments,needed
R9161 T12866 T12865 auxpass are,needed
R9162 T12715 T12714 pobj swimming,of
R9163 T12867 T12868 aux to,distinguish
R9164 T12868 T12865 advcl distinguish,needed
R9165 T12869 T12868 prep between,distinguish
R9166 T12716 T12712 prep near,patterns
R9167 T12870 T12871 det these,possibilities
R9168 T12871 T12869 pobj possibilities,between
R9169 T12717 T12718 det the,edge
R9170 T12872 T12865 punct .,needed
R9171 T12874 T12875 prep In,demonstrate
R9172 T12718 T12716 pobj edge,near
R9173 T12876 T12874 pobj summary,In
R9174 T12719 T12718 prep of,edge
R9175 T12877 T12875 punct ", ",demonstrate
R9176 T12878 T12875 nsubj we,demonstrate
R9177 T12720 T12721 det the,tank
R9178 T12879 T12880 mark that,halts
R9179 T12880 T12875 ccomp halts,demonstrate
R9180 T12721 T12719 pobj tank,of
R9181 T12881 T12880 csubj abrogating,halts
R9182 T12882 T12883 compound Aβ,production
R9183 T12883 T12881 dobj production,abrogating
R9184 T12934 T12932 advcl limit,therapies
R9185 T12884 T12885 det the,progression
R9186 T12885 T12880 dobj progression,halts
R9187 T12886 T12885 prep of,progression
R9188 T12887 T12888 amod pathologic,changes
R9189 T12935 T12936 compound Aβ,production
R9190 T12888 T12886 pobj changes,of
R9191 T12889 T12885 prep in,progression
R9192 T12890 T12891 det a,model
R9193 T12936 T12934 dobj production,limit
R9194 T12891 T12889 pobj model,in
R9195 T12892 T12891 amod transgenic,model
R9196 T12937 T12934 punct ", ",limit
R9197 T12893 T12891 compound mouse,model
R9198 T12894 T12891 prep of,model
R9199 T12895 T12896 compound Alzheimer,type
R9200 T12938 T12934 conj increase,limit
R9201 T12896 T12898 compound type,amyloidosis
R9202 T12897 T12896 punct -,type
R9203 T12898 T12894 pobj amyloidosis,of
R9204 T12939 T12940 compound Aβ,degradation
R9205 T12899 T12875 punct .,demonstrate
R9206 T12901 T12902 advmod However,are
R9207 T12940 T12938 dobj degradation,increase
R9208 T12903 T12902 punct ", ",are
R9209 T12941 T12938 punct ", ",increase
R9210 T12904 T12902 prep despite,are
R9211 T12905 T12906 amod dramatic,reductions
R9212 T12906 T12904 pobj reductions,despite
R9213 T12907 T12906 prep in,reductions
R9214 T12908 T12909 compound Aβ,synthesis
R9215 T12909 T12907 pobj synthesis,in
R9216 T12942 T12938 cc and,increase
R9217 T12910 T12902 punct ", ",are
R9218 T12911 T12912 amod neuritic,plaques
R9219 T12943 T12938 conj enhance,increase
R9220 T12912 T12902 nsubj plaques,are
R9221 T12913 T12914 amod stable,structures
R9222 T12914 T12902 attr structures,are
R9223 T12944 T12943 dobj phagocytosis,enhance
R9224 T12915 T12916 advmod in,vivo
R9225 T12916 T12914 advmod vivo,structures
R9226 T12945 T12944 prep of,phagocytosis
R9227 T12917 T12918 dep that,disaggregate
R9228 T12918 T12914 relcl disaggregate,structures
R9229 T12919 T12918 aux do,disaggregate
R9230 T12946 T12947 amod deposited,amyloid
R9231 T12920 T12918 neg not,disaggregate
R9232 T12921 T12918 advmod quickly,disaggregate
R9233 T12947 T12945 pobj amyloid,of
R9234 T12922 T12902 punct .,are
R9235 T12948 T12928 aux may,required
R9236 T12924 T12925 nsubj It,is
R9237 T12926 T12925 acomp possible,is
R9238 T12949 T12928 auxpass be,required
R9239 T12927 T12928 mark that,required
R9240 T12928 T12925 ccomp required,is
R9241 T12929 T12930 det a,combination
R9242 T12950 T12951 aux to,reverse
R9243 T12930 T12928 nsubjpass combination,required
R9244 T12931 T12930 prep of,combination
R9245 T12951 T12928 advcl reverse,required
R9246 T12932 T12931 pobj therapies,of
R9247 T12933 T12934 aux to,limit
R9248 T12952 T12951 dobj damage,reverse
R9249 T12953 T12952 acl associated,damage
R9250 T12954 T12953 prep with,associated
R9251 T13040 T13028 auxpass be,required
R9252 T12955 T12954 pobj AD,with
R9253 T12956 T12925 punct .,is
R9254 T13041 T13042 aux to,determine
R9255 T13042 T13028 advcl determine,required
R9256 T12958 T12959 advmod However,provide
R9257 T13043 T13044 mark whether,has
R9258 T13044 T13042 ccomp has,determine
R9259 T13045 T13046 det the,brain
R9260 T12960 T12959 punct ", ",provide
R9261 T13046 T13044 nsubj brain,has
R9262 T13047 T13046 amod human,brain
R9263 T13048 T13049 det the,capacity
R9264 T12961 T12962 mark if,started
R9265 T13049 T13044 dobj capacity,has
R9266 T12962 T12959 advcl started,provide
R9267 T13050 T13051 aux to,repair
R9268 T13051 T13049 acl repair,capacity
R9269 T12963 T12964 advmod early,enough
R9270 T13052 T13053 npadvmod amyloid,associated
R9271 T13053 T13055 amod associated,damage
R9272 T13054 T13053 punct -,associated
R9273 T12964 T12962 advmod enough,started
R9274 T13055 T13051 dobj damage,repair
R9275 T13056 T13055 prep of,damage
R9276 T13057 T13056 pobj AD,of
R9277 T12965 T12962 prep in,started
R9278 T13058 T13059 mark once,arrested
R9279 T13059 T13051 advcl arrested,repair
R9280 T12966 T12967 det the,course
R9281 T13060 T13061 det the,progression
R9282 T13061 T13059 nsubjpass progression,arrested
R9283 T13062 T13061 prep of,progression
R9284 T12967 T12965 pobj course,in
R9285 T13063 T13062 pobj pathology,of
R9286 T13064 T13059 auxpass is,arrested
R9287 T13065 T13028 punct .,required
R9288 T12968 T12967 prep of,course
R9289 T12969 T12968 pobj disease,of
R9290 T12970 T12959 punct ", ",provide
R9291 T12971 T12972 compound secretase,inhibitors
R9292 T12972 T12959 nsubj inhibitors,provide
R9293 T12973 T12972 advmod alone,inhibitors
R9294 T12974 T12959 aux could,provide
R9295 T12975 T12976 amod substantial,benefit
R9296 T12976 T12959 dobj benefit,provide
R9297 T12977 T12976 prep in,benefit
R9298 T12978 T12977 pcomp slowing,in
R9299 T12979 T12980 amod pathogenic,processes
R9300 T12980 T12978 dobj processes,slowing
R9301 T12981 T12980 acl linked,processes
R9302 T12982 T12981 prep to,linked
R9303 T12983 T12984 compound amyloid,deposition
R9304 T12984 T12982 pobj deposition,to
R9305 T12985 T12959 punct .,provide
R9306 T12987 T12988 advmod Even,at
R9307 T12988 T12989 prep at,suggests
R9308 T12990 T12991 amod later,stages
R9309 T12991 T12988 pobj stages,at
R9310 T12992 T12991 prep in,stages
R9311 T12993 T12994 det the,disease
R9312 T12994 T12992 pobj disease,in
R9313 T12995 T12989 punct ", ",suggests
R9314 T12996 T12997 det the,presence
R9315 T12997 T12989 nsubj presence,suggests
R9316 T12998 T12997 prep of,presence
R9317 T12999 T13000 amod substantial,activation
R9318 T13000 T12998 pobj activation,of
R9319 T13001 T13000 amod microglial,activation
R9320 T13002 T12997 prep in,presence
R9321 T13003 T13004 amod human,AD
R9322 T13004 T13002 pobj AD,in
R9323 T13005 T13006 punct [,40
R9324 T13006 T13004 parataxis 40,AD
R9325 T13007 T13006 punct ],40
R9326 T13008 T13009 mark that,allow
R9327 T13009 T12989 ccomp allow,suggests
R9328 T13010 T13011 advmod simply,slowing
R9329 T13011 T13009 csubj slowing,allow
R9330 T13012 T13013 det the,formation
R9331 T13013 T13011 dobj formation,slowing
R9332 T13014 T13013 prep of,formation
R9333 T13015 T13016 amod new,deposits
R9334 T13016 T13014 pobj deposits,of
R9335 T13017 T13016 compound amyloid,deposits
R9336 T13018 T13009 aux may,allow
R9337 T13019 T13020 amod ongoing,phagocytosis
R9338 T13020 T13021 nsubj phagocytosis,diminish
R9339 T13021 T13009 ccomp diminish,allow
R9340 T13022 T13021 aux to,diminish
R9341 T13023 T13024 amod preexisting,lesions
R9342 T13024 T13021 dobj lesions,diminish
R9343 T13025 T12989 punct .,suggests
R9344 T13027 T13028 advmod However,required
R9345 T13029 T13028 punct ", ",required
R9346 T13030 T13031 det the,development
R9347 T13031 T13028 nsubjpass development,required
R9348 T13032 T13031 prep of,development
R9349 T13033 T13034 amod safe,inhibitors
R9350 T13034 T13032 pobj inhibitors,of
R9351 T13035 T13033 cc and,safe
R9352 T13036 T13033 conj effective,safe
R9353 T13037 T13034 compound secretase,inhibitors
R9354 T13038 T13028 aux will,required
R9355 T13039 T13028 advmod ultimately,required