PMC:7523471 / 5693-8009 JSONTXT

{"project":"TEST0","denotations":[{"id":"33041751-210-218-816236","span":{"begin":210,"end":214},"obj":"[\"18359102\"]"},{"id":"33041751-229-237-816237","span":{"begin":229,"end":233},"obj":"[\"24861166\"]"},{"id":"33041751-234-242-816238","span":{"begin":246,"end":250},"obj":"[\"32082319\"]"},{"id":"33041751-230-238-816239","span":{"begin":288,"end":292},"obj":"[\"26458742\"]"},{"id":"33041751-233-241-816240","span":{"begin":308,"end":312},"obj":"[\"30559478\"]"},{"id":"33041751-92-100-816241","span":{"begin":407,"end":411},"obj":"[\"3551211\"]"},{"id":"33041751-233-241-816242","span":{"begin":646,"end":650},"obj":"[\"16960575\"]"},{"id":"33041751-227-235-816243","span":{"begin":911,"end":915},"obj":"[\"28197669\"]"},{"id":"33041751-232-240-816244","span":{"begin":936,"end":940},"obj":"[\"29775591\"]"},{"id":"33041751-235-243-816245","span":{"begin":959,"end":963},"obj":"[\"31907265\"]"},{"id":"33041751-218-226-816246","span":{"begin":1394,"end":1398},"obj":"[\"16476660\"]"},{"id":"33041751-226-234-816247","span":{"begin":1417,"end":1421},"obj":"[\"17623022\"]"},{"id":"33041751-231-239-816248","span":{"begin":1447,"end":1451},"obj":"[\"19780903\"]"},{"id":"33041751-234-242-816249","span":{"begin":1468,"end":1472},"obj":"[\"20660248\"]"},{"id":"33041751-233-241-816250","span":{"begin":1492,"end":1496},"obj":"[\"24487585\"]"},{"id":"33041751-224-232-816251","span":{"begin":1514,"end":1518},"obj":"[\"26049087\"]"},{"id":"33041751-227-235-816252","span":{"begin":1540,"end":1544},"obj":"[\"28860067\"]"},{"id":"33041751-235-243-816253","span":{"begin":1570,"end":1574},"obj":"[\"31794021\"]"},{"id":"33041751-226-234-816254","span":{"begin":1587,"end":1591},"obj":"[\"32082319\"]"},{"id":"33041751-226-234-816255","span":{"begin":1846,"end":1850},"obj":"[\"16100572\"]"},{"id":"33041751-234-242-816256","span":{"begin":1869,"end":1873},"obj":"[\"16864778\"]"},{"id":"33041751-229-237-816257","span":{"begin":1892,"end":1896},"obj":"[\"21969301\"]"},{"id":"33041751-235-243-816258","span":{"begin":1912,"end":1916},"obj":"[\"24088808\"]"},{"id":"33041751-233-241-816259","span":{"begin":1934,"end":1938},"obj":"[\"24793238\"]"},{"id":"33041751-228-236-816260","span":{"begin":1956,"end":1960},"obj":"[\"26049087\"]"},{"id":"33041751-235-243-816261","span":{"begin":1977,"end":1981},"obj":"[\"26779813\"]"},{"id":"33041751-235-243-816262","span":{"begin":2007,"end":2011},"obj":"[\"31794021\"]"},{"id":"33041751-227-235-816263","span":{"begin":2032,"end":2036},"obj":"[\"30692527\"]"},{"id":"33041751-230-238-816264","span":{"begin":2049,"end":2053},"obj":"[\"32082319\"]"}],"text":"In addition to the pathology described above, examination of postmortem AD brains demonstrated the existence and propagation of intra- and extracellular, soluble and synaptotoxic forms of Aβ oligomers (Selkoe, 2008; Meli et al., 2014; Li et al., 2020) and pTau assemblies (Takeda et al., 2015; Klein et al., 2019). Other key features of AD neuropathology include cerebral amyloid angiopathy (CAA) (Vinters, 1987) and neuroinflammation – the latter usually involving prolonged activation of microglia and astrocytes, release of pro-inflammatory cytokines and chemokines, as well as infiltration of peripheral immune cells [reviewed in Wyss-Coray (2006)]. In recent decades, cumulative evidence supporting the neuroprotective effects of certain immune cell types and inflammatory mediators have caused a historic shift in the view of neuroinflammation away from the common, merely detrimental one (Zuroff et al., 2017; Deczkowska et al., 2018; Schwartz et al., 2020). In this regard, studies showed that subtypes of bone marrow (BM)-isolated peripheral innate immune cells (e.g., BM-derived CD115+Ly6ChiCD45hi monocytes) can be recruited to the diseased brain of AD-model mice. Interestingly, the recruited cells were shown to directly facilitate Aβ clearance, reduce chronic and detrimental inflammation including scar tissue proteins, and induce synaptogenesis and neurogenesis (Simard et al., 2006; Butovsky et al., 2007; Koronyo-Hamaoui et al., 2009; Lebson et al., 2010; Bernstein et al., 2014; Koronyo et al., 2015; Rentsendorj et al., 2018; Koronyo-Hamaoui et al., 2019; Li et al., 2020). These and other promising multi-targeted immunomodulatory strategies of harnessing peripheral immune cells to fight neurodegeneration are currently being developed and tested in various preclinical and clinical trials across the world (Frenkel et al., 2005; Butovsky et al., 2006; Bakalash et al., 2011; Kunis et al., 2013; Villeda et al., 2014; Koronyo et al., 2015; Baruch et al., 2016; Koronyo-Hamaoui et al., 2019; Rosenzweig et al., 2019; Li et al., 2020). Despite these advances, limitations persist due to the lack of readily available in vivo approaches to noninvasively and accurately monitor therapeutic efficacy, motivating scientists to search for new tools that can be widely deployed in the clinical setting."}

{"project":"2_test","denotations":[{"id":"33041751-18359102-38666022","span":{"begin":210,"end":214},"obj":"18359102"},{"id":"33041751-24861166-38666023","span":{"begin":229,"end":233},"obj":"24861166"},{"id":"33041751-32082319-38666024","span":{"begin":246,"end":250},"obj":"32082319"},{"id":"33041751-26458742-38666025","span":{"begin":288,"end":292},"obj":"26458742"},{"id":"33041751-30559478-38666026","span":{"begin":308,"end":312},"obj":"30559478"},{"id":"33041751-3551211-38666027","span":{"begin":407,"end":411},"obj":"3551211"},{"id":"33041751-16960575-38666028","span":{"begin":646,"end":650},"obj":"16960575"},{"id":"33041751-28197669-38666029","span":{"begin":911,"end":915},"obj":"28197669"},{"id":"33041751-29775591-38666030","span":{"begin":936,"end":940},"obj":"29775591"},{"id":"33041751-31907265-38666031","span":{"begin":959,"end":963},"obj":"31907265"},{"id":"33041751-16476660-38666032","span":{"begin":1394,"end":1398},"obj":"16476660"},{"id":"33041751-17623022-38666033","span":{"begin":1417,"end":1421},"obj":"17623022"},{"id":"33041751-19780903-38666034","span":{"begin":1447,"end":1451},"obj":"19780903"},{"id":"33041751-20660248-38666035","span":{"begin":1468,"end":1472},"obj":"20660248"},{"id":"33041751-24487585-38666036","span":{"begin":1492,"end":1496},"obj":"24487585"},{"id":"33041751-26049087-38666037","span":{"begin":1514,"end":1518},"obj":"26049087"},{"id":"33041751-28860067-38666038","span":{"begin":1540,"end":1544},"obj":"28860067"},{"id":"33041751-31794021-38666039","span":{"begin":1570,"end":1574},"obj":"31794021"},{"id":"33041751-32082319-38666040","span":{"begin":1587,"end":1591},"obj":"32082319"},{"id":"33041751-16100572-38666041","span":{"begin":1846,"end":1850},"obj":"16100572"},{"id":"33041751-16864778-38666042","span":{"begin":1869,"end":1873},"obj":"16864778"},{"id":"33041751-21969301-38666043","span":{"begin":1892,"end":1896},"obj":"21969301"},{"id":"33041751-24088808-38666044","span":{"begin":1912,"end":1916},"obj":"24088808"},{"id":"33041751-24793238-38666045","span":{"begin":1934,"end":1938},"obj":"24793238"},{"id":"33041751-26049087-38666046","span":{"begin":1956,"end":1960},"obj":"26049087"},{"id":"33041751-26779813-38666047","span":{"begin":1977,"end":1981},"obj":"26779813"},{"id":"33041751-31794021-38666048","span":{"begin":2007,"end":2011},"obj":"31794021"},{"id":"33041751-30692527-38666049","span":{"begin":2032,"end":2036},"obj":"30692527"},{"id":"33041751-32082319-38666050","span":{"begin":2049,"end":2053},"obj":"32082319"}],"text":"In addition to the pathology described above, examination of postmortem AD brains demonstrated the existence and propagation of intra- and extracellular, soluble and synaptotoxic forms of Aβ oligomers (Selkoe, 2008; Meli et al., 2014; Li et al., 2020) and pTau assemblies (Takeda et al., 2015; Klein et al., 2019). Other key features of AD neuropathology include cerebral amyloid angiopathy (CAA) (Vinters, 1987) and neuroinflammation – the latter usually involving prolonged activation of microglia and astrocytes, release of pro-inflammatory cytokines and chemokines, as well as infiltration of peripheral immune cells [reviewed in Wyss-Coray (2006)]. In recent decades, cumulative evidence supporting the neuroprotective effects of certain immune cell types and inflammatory mediators have caused a historic shift in the view of neuroinflammation away from the common, merely detrimental one (Zuroff et al., 2017; Deczkowska et al., 2018; Schwartz et al., 2020). In this regard, studies showed that subtypes of bone marrow (BM)-isolated peripheral innate immune cells (e.g., BM-derived CD115+Ly6ChiCD45hi monocytes) can be recruited to the diseased brain of AD-model mice. Interestingly, the recruited cells were shown to directly facilitate Aβ clearance, reduce chronic and detrimental inflammation including scar tissue proteins, and induce synaptogenesis and neurogenesis (Simard et al., 2006; Butovsky et al., 2007; Koronyo-Hamaoui et al., 2009; Lebson et al., 2010; Bernstein et al., 2014; Koronyo et al., 2015; Rentsendorj et al., 2018; Koronyo-Hamaoui et al., 2019; Li et al., 2020). These and other promising multi-targeted immunomodulatory strategies of harnessing peripheral immune cells to fight neurodegeneration are currently being developed and tested in various preclinical and clinical trials across the world (Frenkel et al., 2005; Butovsky et al., 2006; Bakalash et al., 2011; Kunis et al., 2013; Villeda et al., 2014; Koronyo et al., 2015; Baruch et al., 2016; Koronyo-Hamaoui et al., 2019; Rosenzweig et al., 2019; Li et al., 2020). Despite these advances, limitations persist due to the lack of readily available in vivo approaches to noninvasively and accurately monitor therapeutic efficacy, motivating scientists to search for new tools that can be widely deployed in the clinical setting."}

{"project":"0_colil","denotations":[{"id":"33041751-18359102-816236","span":{"begin":210,"end":214},"obj":"18359102"},{"id":"33041751-24861166-816237","span":{"begin":229,"end":233},"obj":"24861166"},{"id":"33041751-32082319-816238","span":{"begin":246,"end":250},"obj":"32082319"},{"id":"33041751-26458742-816239","span":{"begin":288,"end":292},"obj":"26458742"},{"id":"33041751-30559478-816240","span":{"begin":308,"end":312},"obj":"30559478"},{"id":"33041751-3551211-816241","span":{"begin":407,"end":411},"obj":"3551211"},{"id":"33041751-16960575-816242","span":{"begin":646,"end":650},"obj":"16960575"},{"id":"33041751-28197669-816243","span":{"begin":911,"end":915},"obj":"28197669"},{"id":"33041751-29775591-816244","span":{"begin":936,"end":940},"obj":"29775591"},{"id":"33041751-31907265-816245","span":{"begin":959,"end":963},"obj":"31907265"},{"id":"33041751-16476660-816246","span":{"begin":1394,"end":1398},"obj":"16476660"},{"id":"33041751-17623022-816247","span":{"begin":1417,"end":1421},"obj":"17623022"},{"id":"33041751-19780903-816248","span":{"begin":1447,"end":1451},"obj":"19780903"},{"id":"33041751-20660248-816249","span":{"begin":1468,"end":1472},"obj":"20660248"},{"id":"33041751-24487585-816250","span":{"begin":1492,"end":1496},"obj":"24487585"},{"id":"33041751-26049087-816251","span":{"begin":1514,"end":1518},"obj":"26049087"},{"id":"33041751-28860067-816252","span":{"begin":1540,"end":1544},"obj":"28860067"},{"id":"33041751-31794021-816253","span":{"begin":1570,"end":1574},"obj":"31794021"},{"id":"33041751-32082319-816254","span":{"begin":1587,"end":1591},"obj":"32082319"},{"id":"33041751-16100572-816255","span":{"begin":1846,"end":1850},"obj":"16100572"},{"id":"33041751-16864778-816256","span":{"begin":1869,"end":1873},"obj":"16864778"},{"id":"33041751-21969301-816257","span":{"begin":1892,"end":1896},"obj":"21969301"},{"id":"33041751-24088808-816258","span":{"begin":1912,"end":1916},"obj":"24088808"},{"id":"33041751-24793238-816259","span":{"begin":1934,"end":1938},"obj":"24793238"},{"id":"33041751-26049087-816260","span":{"begin":1956,"end":1960},"obj":"26049087"},{"id":"33041751-26779813-816261","span":{"begin":1977,"end":1981},"obj":"26779813"},{"id":"33041751-31794021-816262","span":{"begin":2007,"end":2011},"obj":"31794021"},{"id":"33041751-30692527-816263","span":{"begin":2032,"end":2036},"obj":"30692527"},{"id":"33041751-32082319-816264","span":{"begin":2049,"end":2053},"obj":"32082319"}],"text":"In addition to the pathology described above, examination of postmortem AD brains demonstrated the existence and propagation of intra- and extracellular, soluble and synaptotoxic forms of Aβ oligomers (Selkoe, 2008; Meli et al., 2014; Li et al., 2020) and pTau assemblies (Takeda et al., 2015; Klein et al., 2019). Other key features of AD neuropathology include cerebral amyloid angiopathy (CAA) (Vinters, 1987) and neuroinflammation – the latter usually involving prolonged activation of microglia and astrocytes, release of pro-inflammatory cytokines and chemokines, as well as infiltration of peripheral immune cells [reviewed in Wyss-Coray (2006)]. In recent decades, cumulative evidence supporting the neuroprotective effects of certain immune cell types and inflammatory mediators have caused a historic shift in the view of neuroinflammation away from the common, merely detrimental one (Zuroff et al., 2017; Deczkowska et al., 2018; Schwartz et al., 2020). In this regard, studies showed that subtypes of bone marrow (BM)-isolated peripheral innate immune cells (e.g., BM-derived CD115+Ly6ChiCD45hi monocytes) can be recruited to the diseased brain of AD-model mice. Interestingly, the recruited cells were shown to directly facilitate Aβ clearance, reduce chronic and detrimental inflammation including scar tissue proteins, and induce synaptogenesis and neurogenesis (Simard et al., 2006; Butovsky et al., 2007; Koronyo-Hamaoui et al., 2009; Lebson et al., 2010; Bernstein et al., 2014; Koronyo et al., 2015; Rentsendorj et al., 2018; Koronyo-Hamaoui et al., 2019; Li et al., 2020). These and other promising multi-targeted immunomodulatory strategies of harnessing peripheral immune cells to fight neurodegeneration are currently being developed and tested in various preclinical and clinical trials across the world (Frenkel et al., 2005; Butovsky et al., 2006; Bakalash et al., 2011; Kunis et al., 2013; Villeda et al., 2014; Koronyo et al., 2015; Baruch et al., 2016; Koronyo-Hamaoui et al., 2019; Rosenzweig et al., 2019; Li et al., 2020). Despite these advances, limitations persist due to the lack of readily available in vivo approaches to noninvasively and accurately monitor therapeutic efficacy, motivating scientists to search for new tools that can be widely deployed in the clinical setting."}