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18F-AV-1451 Positron Emission Tomography in Neuropathological Substrates of Corticobasal Syndrome

Brain(2020)

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摘要
Multiple neuropathological processes can manifest in life as a corticobasal syndrome. We sought to relate retention of the tau-PET tracer F-18-AV-1451 and structural magnetic resonance measures of regional atrophy to clinical features in clinically diagnosed and neuropathologically confirmed cases of corticobasal syndrome and to determine whether these vary with the underlying neuropathological changes. In this observational, cross-sectional study, 11 subjects (eight female and three male, median age 72 years) with corticobasal syndrome underwent structural MRI, tau-PET with F-18-AV-1451, amyloid-PET with C-11-Pittsburgh compound B, detailed clinical examinations and neuropsychological testing. Of the 11, three had evidence of high amyloid burden consistent with Alzheimer's disease while eight did not. Neuropathological evaluations were acquired in six cases. Mixed effects general linear models were used to compare F-18-AV-1451 retention and atrophy in amyloid-negative corticobasal syndrome cases to 32 age-matched healthy control subjects and to relate cortical and subcortical F-18-AV-1451 retention and atrophy to clinical features. Subjects without amyloid, including three with pathologically confirmed corticobasal degeneration, showed greater regional F-18-AV-1451 retention and associated regional atrophy in areas commonly associated with corticobasal degeneration pathology than healthy control subjects [retention was higher compared to healthy controls (P = 0.0011), driven especially by the precentral gyrus (P = 0.011) and pallidum (P<0.0001), and greater atrophy was seen in subjects compared to control subjects (P = 0.0004)]. Both F-18-AV-1451 retention and atrophy were greater in the clinically more affected hemisphere [on average, retention was 0.173 standardized uptake value ratio units higher on the more affected side (95% confidence interval, CI 0.11-0.24, P<0.0001), and volume was 0.719 lower on the more affected side (95% CI 0.35-1.08, P = 0.0001)]. F-18-AV-1451 retention was greater in subcortical than in cortical regions, P<0.0001. In contrast to these findings, subjects with amyloid-positive corticobasal syndrome, including two neuropathologically confirmed cases of Alzheimer's disease, demonstrated greater and more widespread F-18-AV-1451 retention and regional atrophy than observed in the amyloid-negative cases. There was thalamic F-18-AV-1451 retention but minimal cortical and basal ganglia uptake in a single corticobasal syndrome subject without neuropathological evidence of tau pathology, likely representing non-specific signal. Asymmetric cortical and basal ganglia F-18-AV-1451 retention consonant with the clinical manifestations characterize corticobasal syndrome due to corticobasal degeneration, whereas the cortical retention in cases associated with Alzheimer's disease is greater and more diffuse.
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关键词
corticobasal degeneration,corticobasal syndrome,AV-1451,tau-PET
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