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

INTRODUCTION: F-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: ] = 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.