Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
Correlation between in vivo 18F-flortaucipir PET and whole-brain postmortem histological tau signals in Alzheimer's disease.
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Chao Yishu, Chen Yuheng, Chadwick Trevor A, Harrison Theresa M, Iaccarino Leonardo, Heinsen Helmut, Ushizima Daniela, Tosun Duygu, Jagust William J, Grinberg Lea T
Аннотация
INTRODUCTION: Clinicopathological studies offer crucial interpretations of 18F-flortaucipir (FTP) tau positron emission tomography (PET) signal but are limited by methods. We leveraged whole-brain, quantitative immunohistochemical (IHC) Alzheimer's Disease (AD) tau density maps to comprehensively evaluate the FTP tracer.
METHODS: We generated IHC maps for three AD-tau antibodies-AT8, AT100, and MC1-using two human brains histologically staged at Braak IV and VI. FTP-PET scans were acquired 6 and 10 weeks prior to death. Using region-wise and voxelwise methods, we correlated FTP-PET with IHC signals.
RESULTS: Only AT8 (p-tau Ser202/Thr205; neuronal and neuritic tau pathology) showed a notable correlation with FTP standardized uptake value ratios (SUVRs) in the Braak VI case (Spearman's rank correlation coefficient [rs] = 0.461, p < 0.001). FTP SUVRs failed to capture medial temporal lobe (MTL) tau burden, whereas neocortical regions showed lower IHC burden but more variability in FTP uptake.
DISCUSSION: Although FTP signals correlate well with AT8-positive tau in the more advanced case, they underestimate the severity of MTL burden, potentially confounding assessments of tau-targeted therapies.
METHODS: We generated IHC maps for three AD-tau antibodies-AT8, AT100, and MC1-using two human brains histologically staged at Braak IV and VI. FTP-PET scans were acquired 6 and 10 weeks prior to death. Using region-wise and voxelwise methods, we correlated FTP-PET with IHC signals.
RESULTS: Only AT8 (p-tau Ser202/Thr205; neuronal and neuritic tau pathology) showed a notable correlation with FTP standardized uptake value ratios (SUVRs) in the Braak VI case (Spearman's rank correlation coefficient [rs] = 0.461, p < 0.001). FTP SUVRs failed to capture medial temporal lobe (MTL) tau burden, whereas neocortical regions showed lower IHC burden but more variability in FTP uptake.
DISCUSSION: Although FTP signals correlate well with AT8-positive tau in the more advanced case, they underestimate the severity of MTL burden, potentially confounding assessments of tau-targeted therapies.