PMC:7523471 / 26000-28117 JSONTXT

{"project":"TEST0","denotations":[{"id":"33041751-232-240-816371","span":{"begin":265,"end":269},"obj":"[\"3736630\"]"},{"id":"33041751-228-236-816372","span":{"begin":286,"end":290},"obj":"[\"2819446\"]"},{"id":"33041751-142-150-816373","span":{"begin":435,"end":439},"obj":"[\"23714377\"]"},{"id":"33041751-165-173-816374","span":{"begin":458,"end":462},"obj":"[\"28379416\"]"},{"id":"33041751-227-235-816375","span":{"begin":650,"end":654},"obj":"[\"23300938\"]"},{"id":"33041751-87-95-816376","span":{"begin":744,"end":748},"obj":"[\"30593285\"]"},{"id":"33041751-110-118-816377","span":{"begin":767,"end":771},"obj":"[\"31551688\"]"},{"id":"33041751-234-242-816378","span":{"begin":1138,"end":1142},"obj":"[\"23300938\"]"},{"id":"33041751-226-234-816379","span":{"begin":1161,"end":1165},"obj":"[\"30593285\"]"},{"id":"33041751-189-197-816381","span":{"begin":1623,"end":1627},"obj":"[\"30593285\"]"},{"id":"33041751-158-166-816382","span":{"begin":2111,"end":2115},"obj":"[\"30593285\"]"}],"text":"Initial post-mortem examinations of late-stage AD retinas did not reveal neurofibrillary inclusions, neuritic plaques or amyloid angiopathy, despite histological observations of GCL degeneration, reduced NFL thickness and optic nerve axonal atrophy (Hinton et al., 1986; Blanks et al., 1989). While a limited number of studies have been unable to histopathologically detect abnormal tau accumulation in retinas of patients (Ho et al., 2014; Williams et al., 2017), the first evidence of disease-associated tau hyperphosphorylation in post-mortem retinas of confirmed AD cases was reported by Schön and colleagues in 2012 (Figures 4A,B; Schön et al., 2012). Results from this study were corroborated thereafter by other groups (den Haan et al., 2018; Grimaldi et al., 2019). Different pTau species, recognized by phosphorylation site-specific antibodies such as AT8 (pSer202, pThr205), AT100 (pThr212 and pSer214), and AT270 (pThr181), were primarily found in the inner retinal layers, particularly the plexiform layers, INL, and GCL of AD patients, thus closely mirroring the physiological expression pattern of normal tau (Schön et al., 2012; den Haan et al., 2018). Interestingly, a recent independent report on a quantitative histomorphometric analysis of post-mortem tissue revealed that these particular retinal layers undergo significant pathological atrophy in AD compared to non-demented control cases (Asanad et al., 2019b). Geometric analysis of postmortem retinal tissue from 6 control cases and 6 AD patients showed more intense AT8-immunoreactivity in superior than in medial retinal regions (den Haan et al., 2018). Qualitative observations from the same study also showed a positive gradient away from the optic nerve and toward the periphery. Despite the presence of pTau in all 6 AD retinas, no significant difference was found in retinal pTau area coverage between the two diagnostic groups, likely due to 2 outliers in control cases. Importantly, a novel and significant association was also found between retinal AT8 burden and cerebral amyloid plaque but not NFT severity (den Haan et al., 2018)."}

{"project":"2_test","denotations":[{"id":"33041751-3736630-38666157","span":{"begin":265,"end":269},"obj":"3736630"},{"id":"33041751-2819446-38666158","span":{"begin":286,"end":290},"obj":"2819446"},{"id":"33041751-23714377-38666159","span":{"begin":435,"end":439},"obj":"23714377"},{"id":"33041751-28379416-38666160","span":{"begin":458,"end":462},"obj":"28379416"},{"id":"33041751-23300938-38666161","span":{"begin":650,"end":654},"obj":"23300938"},{"id":"33041751-30593285-38666162","span":{"begin":744,"end":748},"obj":"30593285"},{"id":"33041751-31551688-38666163","span":{"begin":767,"end":771},"obj":"31551688"},{"id":"33041751-23300938-38666164","span":{"begin":1138,"end":1142},"obj":"23300938"},{"id":"33041751-30593285-38666165","span":{"begin":1161,"end":1165},"obj":"30593285"},{"id":"33041751-30593285-38666167","span":{"begin":1623,"end":1627},"obj":"30593285"},{"id":"33041751-30593285-38666168","span":{"begin":2111,"end":2115},"obj":"30593285"}],"text":"Initial post-mortem examinations of late-stage AD retinas did not reveal neurofibrillary inclusions, neuritic plaques or amyloid angiopathy, despite histological observations of GCL degeneration, reduced NFL thickness and optic nerve axonal atrophy (Hinton et al., 1986; Blanks et al., 1989). While a limited number of studies have been unable to histopathologically detect abnormal tau accumulation in retinas of patients (Ho et al., 2014; Williams et al., 2017), the first evidence of disease-associated tau hyperphosphorylation in post-mortem retinas of confirmed AD cases was reported by Schön and colleagues in 2012 (Figures 4A,B; Schön et al., 2012). Results from this study were corroborated thereafter by other groups (den Haan et al., 2018; Grimaldi et al., 2019). Different pTau species, recognized by phosphorylation site-specific antibodies such as AT8 (pSer202, pThr205), AT100 (pThr212 and pSer214), and AT270 (pThr181), were primarily found in the inner retinal layers, particularly the plexiform layers, INL, and GCL of AD patients, thus closely mirroring the physiological expression pattern of normal tau (Schön et al., 2012; den Haan et al., 2018). Interestingly, a recent independent report on a quantitative histomorphometric analysis of post-mortem tissue revealed that these particular retinal layers undergo significant pathological atrophy in AD compared to non-demented control cases (Asanad et al., 2019b). Geometric analysis of postmortem retinal tissue from 6 control cases and 6 AD patients showed more intense AT8-immunoreactivity in superior than in medial retinal regions (den Haan et al., 2018). Qualitative observations from the same study also showed a positive gradient away from the optic nerve and toward the periphery. Despite the presence of pTau in all 6 AD retinas, no significant difference was found in retinal pTau area coverage between the two diagnostic groups, likely due to 2 outliers in control cases. Importantly, a novel and significant association was also found between retinal AT8 burden and cerebral amyloid plaque but not NFT severity (den Haan et al., 2018)."}

{"project":"0_colil","denotations":[{"id":"33041751-3736630-816371","span":{"begin":265,"end":269},"obj":"3736630"},{"id":"33041751-2819446-816372","span":{"begin":286,"end":290},"obj":"2819446"},{"id":"33041751-23714377-816373","span":{"begin":435,"end":439},"obj":"23714377"},{"id":"33041751-28379416-816374","span":{"begin":458,"end":462},"obj":"28379416"},{"id":"33041751-23300938-816375","span":{"begin":650,"end":654},"obj":"23300938"},{"id":"33041751-30593285-816376","span":{"begin":744,"end":748},"obj":"30593285"},{"id":"33041751-31551688-816377","span":{"begin":767,"end":771},"obj":"31551688"},{"id":"33041751-23300938-816378","span":{"begin":1138,"end":1142},"obj":"23300938"},{"id":"33041751-30593285-816379","span":{"begin":1161,"end":1165},"obj":"30593285"},{"id":"33041751-30593285-816381","span":{"begin":1623,"end":1627},"obj":"30593285"},{"id":"33041751-30593285-816382","span":{"begin":2111,"end":2115},"obj":"30593285"}],"text":"Initial post-mortem examinations of late-stage AD retinas did not reveal neurofibrillary inclusions, neuritic plaques or amyloid angiopathy, despite histological observations of GCL degeneration, reduced NFL thickness and optic nerve axonal atrophy (Hinton et al., 1986; Blanks et al., 1989). While a limited number of studies have been unable to histopathologically detect abnormal tau accumulation in retinas of patients (Ho et al., 2014; Williams et al., 2017), the first evidence of disease-associated tau hyperphosphorylation in post-mortem retinas of confirmed AD cases was reported by Schön and colleagues in 2012 (Figures 4A,B; Schön et al., 2012). Results from this study were corroborated thereafter by other groups (den Haan et al., 2018; Grimaldi et al., 2019). Different pTau species, recognized by phosphorylation site-specific antibodies such as AT8 (pSer202, pThr205), AT100 (pThr212 and pSer214), and AT270 (pThr181), were primarily found in the inner retinal layers, particularly the plexiform layers, INL, and GCL of AD patients, thus closely mirroring the physiological expression pattern of normal tau (Schön et al., 2012; den Haan et al., 2018). Interestingly, a recent independent report on a quantitative histomorphometric analysis of post-mortem tissue revealed that these particular retinal layers undergo significant pathological atrophy in AD compared to non-demented control cases (Asanad et al., 2019b). Geometric analysis of postmortem retinal tissue from 6 control cases and 6 AD patients showed more intense AT8-immunoreactivity in superior than in medial retinal regions (den Haan et al., 2018). Qualitative observations from the same study also showed a positive gradient away from the optic nerve and toward the periphery. Despite the presence of pTau in all 6 AD retinas, no significant difference was found in retinal pTau area coverage between the two diagnostic groups, likely due to 2 outliers in control cases. Importantly, a novel and significant association was also found between retinal AT8 burden and cerebral amyloid plaque but not NFT severity (den Haan et al., 2018)."}