Correlation between in vivo 18F-flortaucipir PET and whole-brain postmortem histological tau signals in Alzheimer's disease

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.