PMC:6582309 / 35744-39269 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/6582309","sourcedb":"PMC","sourceid":"6582309","source_url":"https://www.ncbi.nlm.nih.gov/pmc/6582309","text":"Biomarkers\nNeurodegenerative diseases are particularly challenging diseases, as they are difficult to diagnose in the initial stages. Although many years of research have been devoted to the identification of suitable biomarkers, preferably in blood, that would allow early diagnosis or even prediction of AD in humans, such markers remain elusive. Numerous candidates have been identified in both blood and CSF, but none of the markers identified so far have been used routinely in the clinics. CSF levels of Aβ, total TAU and hyperphosphorylated TAU are the most often monitored variables, along with PET molecular imaging of amyloid and TAU deposition, in diagnosis of early stages of AD (McKhann et al., 2011).\nIn dogs there are no biological markers that would allow accurate and early diagnosis of CCD. In most cases assessment of cognitive functions through several neuropsychological tests and excluding other conditions with overlapping symptoms is sufficient to confirm diagnosis when the disease has progressed, but markers for detecting disease in early stages would be very useful in veterinary medicine.\nIn dogs with CCD, plasma Aβ42, a longer Aβ isoform which is more fibrillogenic and associated with disease, was monitored as a biomarker potentially linked to CCD (González-Martínez et al., 2011; Schütt et al., 2015). One study showed highest Aβ42 plasma levels in younger healthy dogs, and significantly higher Aβ42 plasma levels in mildly cognitively impaired dogs in comparison to severely impaired dogs (González-Martínez et al., 2011). However, another study reported the opposite with highest Aβ42 plasma levels in CCD dogs (Schütt et al., 2015). Plasma ratio of Aβ40 and Aβ42, was shown to be similar in human AD and CCD as in healthy individuals (Mayeux et al., 2003; Lopez et al., 2008; González-Martínez et al., 2011) although in some studies decreases in plasma Aβ42 were an indicator of faster progression of CCD and AD (Pesini et al., 2009; González-Martínez et al., 2011). This points to a possible disease mechanism wherein aggregation and accumulation of Aβ in the brain results in lower levels of Aβ in plasma and CSF. A more recent human study showed decrease in plasma Aβ during the dementia stage of AD and increased levels of Aβ in plasma during vascular disease (Janelidze et al., 2016).\nIn healthy aged dogs with age related Aβ deposits, a decrease in levels of Aβ42, but not Aβ40 was detected in CSF (Head et al., 2010). Similarly, in elderly people Aβ42 has been monitored in CSF and the decrease in Aβ42 is suggested as biomarker for Aβ deposition in the brain and has been observed alongside brain atrophy (Fagan et al., 2009; Racine et al., 2016). Although CSF Aβ content decreased in the aging dog (Head et al., 2010), high levels of Aβ in the CSF of young and middle-aged dogs also correlated with impaired learning (Borghys et al., 2017). This infers high CSF Aβ levels in younger dogs, which are not likely to harbor depositions of amyloid in their brains yet, as an early biomarker for the development of cognitive impairment. One study also reported an increase of lactate, pyruvate and potassium concentrations in CSF of dogs correlating with severe cognitive impairment (Pugliese et al., 2005), but this has not been firmly established or confirmed. Therefore, there are no biomarkers available to monitor and predict CCD progress in dogs. Future studies aiming to develop such biomarkers would be needed, hoping to provide biomarkers for early detection of this disease.","divisions":[{"label":"title","span":{"begin":0,"end":10}},{"label":"p","span":{"begin":11,"end":714}},{"label":"p","span":{"begin":715,"end":1117}},{"label":"p","span":{"begin":1118,"end":2327}}],"tracks":[{"project":"2_test","denotations":[{"id":"31249505-21514250-38601666","span":{"begin":708,"end":712},"obj":"21514250"},{"id":"31249505-21377518-38601667","span":{"begin":1308,"end":1312},"obj":"21377518"},{"id":"31249505-26463980-38601668","span":{"begin":1329,"end":1333},"obj":"26463980"},{"id":"31249505-21377518-38601669","span":{"begin":1552,"end":1556},"obj":"21377518"},{"id":"31249505-26463980-38601670","span":{"begin":1664,"end":1668},"obj":"26463980"},{"id":"31249505-14610118-38601671","span":{"begin":1788,"end":1792},"obj":"14610118"},{"id":"31249505-18401021-38601672","span":{"begin":1808,"end":1812},"obj":"18401021"},{"id":"31249505-21377518-38601673","span":{"begin":1840,"end":1844},"obj":"21377518"},{"id":"31249505-21377518-38601674","span":{"begin":1998,"end":2002},"obj":"21377518"},{"id":"31249505-27241045-38601675","span":{"begin":2321,"end":2325},"obj":"27241045"},{"id":"31249505-20164551-38601676","span":{"begin":2456,"end":2460},"obj":"20164551"},{"id":"31249505-19260027-38601677","span":{"begin":2666,"end":2670},"obj":"19260027"},{"id":"31249505-26955655-38601678","span":{"begin":2687,"end":2691},"obj":"26955655"},{"id":"31249505-20164551-38601679","span":{"begin":2759,"end":2763},"obj":"20164551"},{"id":"31249505-28035921-38601680","span":{"begin":2881,"end":2885},"obj":"28035921"},{"id":"31249505-15866364-38601681","span":{"begin":3242,"end":3246},"obj":"15866364"}],"attributes":[{"subj":"31249505-21514250-38601666","pred":"source","obj":"2_test"},{"subj":"31249505-21377518-38601667","pred":"source","obj":"2_test"},{"subj":"31249505-26463980-38601668","pred":"source","obj":"2_test"},{"subj":"31249505-21377518-38601669","pred":"source","obj":"2_test"},{"subj":"31249505-26463980-38601670","pred":"source","obj":"2_test"},{"subj":"31249505-14610118-38601671","pred":"source","obj":"2_test"},{"subj":"31249505-18401021-38601672","pred":"source","obj":"2_test"},{"subj":"31249505-21377518-38601673","pred":"source","obj":"2_test"},{"subj":"31249505-21377518-38601674","pred":"source","obj":"2_test"},{"subj":"31249505-27241045-38601675","pred":"source","obj":"2_test"},{"subj":"31249505-20164551-38601676","pred":"source","obj":"2_test"},{"subj":"31249505-19260027-38601677","pred":"source","obj":"2_test"},{"subj":"31249505-26955655-38601678","pred":"source","obj":"2_test"},{"subj":"31249505-20164551-38601679","pred":"source","obj":"2_test"},{"subj":"31249505-28035921-38601680","pred":"source","obj":"2_test"},{"subj":"31249505-15866364-38601681","pred":"source","obj":"2_test"}]},{"project":"0_colil","denotations":[{"id":"31249505-21514250-737091","span":{"begin":708,"end":712},"obj":"21514250"},{"id":"31249505-21377518-737092","span":{"begin":1308,"end":1312},"obj":"21377518"},{"id":"31249505-26463980-737093","span":{"begin":1329,"end":1333},"obj":"26463980"},{"id":"31249505-21377518-737094","span":{"begin":1552,"end":1556},"obj":"21377518"},{"id":"31249505-26463980-737095","span":{"begin":1664,"end":1668},"obj":"26463980"},{"id":"31249505-14610118-737096","span":{"begin":1788,"end":1792},"obj":"14610118"},{"id":"31249505-18401021-737097","span":{"begin":1808,"end":1812},"obj":"18401021"},{"id":"31249505-21377518-737098","span":{"begin":1840,"end":1844},"obj":"21377518"},{"id":"31249505-21377518-737099","span":{"begin":1998,"end":2002},"obj":"21377518"},{"id":"31249505-27241045-737100","span":{"begin":2321,"end":2325},"obj":"27241045"},{"id":"31249505-20164551-737101","span":{"begin":2456,"end":2460},"obj":"20164551"},{"id":"31249505-19260027-737102","span":{"begin":2666,"end":2670},"obj":"19260027"},{"id":"31249505-26955655-737103","span":{"begin":2687,"end":2691},"obj":"26955655"},{"id":"31249505-20164551-737104","span":{"begin":2759,"end":2763},"obj":"20164551"},{"id":"31249505-28035921-737105","span":{"begin":2881,"end":2885},"obj":"28035921"},{"id":"31249505-15866364-737106","span":{"begin":3242,"end":3246},"obj":"15866364"}],"attributes":[{"subj":"31249505-21514250-737091","pred":"source","obj":"0_colil"},{"subj":"31249505-21377518-737092","pred":"source","obj":"0_colil"},{"subj":"31249505-26463980-737093","pred":"source","obj":"0_colil"},{"subj":"31249505-21377518-737094","pred":"source","obj":"0_colil"},{"subj":"31249505-26463980-737095","pred":"source","obj":"0_colil"},{"subj":"31249505-14610118-737096","pred":"source","obj":"0_colil"},{"subj":"31249505-18401021-737097","pred":"source","obj":"0_colil"},{"subj":"31249505-21377518-737098","pred":"source","obj":"0_colil"},{"subj":"31249505-21377518-737099","pred":"source","obj":"0_colil"},{"subj":"31249505-27241045-737100","pred":"source","obj":"0_colil"},{"subj":"31249505-20164551-737101","pred":"source","obj":"0_colil"},{"subj":"31249505-19260027-737102","pred":"source","obj":"0_colil"},{"subj":"31249505-26955655-737103","pred":"source","obj":"0_colil"},{"subj":"31249505-20164551-737104","pred":"source","obj":"0_colil"},{"subj":"31249505-28035921-737105","pred":"source","obj":"0_colil"},{"subj":"31249505-15866364-737106","pred":"source","obj":"0_colil"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#ecd493","default":true},{"id":"0_colil","color":"#ba93ec"}]}]}}