To evaluate tau PET-to-autopsy correlations in a cross-sectional sample of patients with diverse neurodegenerative pathologies.

Correlation of [18F]Flortaucipir PET (FTP) to autopsy diagnosis and post-mortem tau pathology has been limited.

Fifteen patients with ante-mortem FTP underwent autopsy (mean age 60, standard deviation [S.D.] 14; mean PET-to-autopsy time 27 months, S.D. 15). Neuroimaging: Patient FTP 80-100 minute standardized uptake value ratio (SUVR) images (inferior cerebellar gray matter reference) were compared to SUVR in 88 amyloid-negative, cognitively normal controls (CN; mean age 66, S.D. 20). SUVRs in regions corresponding to Braak stages were compared to 14 young, non-autopsy controls (YC; mean age 26, S.D. 4.6) used as a tau-negative standard. Neuropathology: Blinded autopsies were completed using a research protocol.

Primary autopsy diagnoses included Alzheimer’s disease (AD; n=4), progressive supranuclear palsy (PSP; n=4), corticobasal degeneration (CBD; n=2), FTLD-tau from MAPT mutations (n=2), argyrophilic grain disease (AGD; n=1), TDP-43 type B (n=1), and FTLD-FUS (n=1). Patients with primary AD pathology had intense cortical tracer retention, especially in the parietal lobes, corresponding to tau neurofibrillary tangle (NFT) pathology. CBD patients had distinct tracer retention in frontal white matter and striatum that correlated with tau pathology. Other tauopathies (PSP, AGD, FTLD-tau) and FTLD-TDP/FUS showed mildly elevated FTP binding compared to CNs, often in areas of severe neurodegeneration. Patients with primary AD pathology (Braak VI) had elevated SUVRs across all regions compared to other patients and YCs (p<0.001, each region). Patients with Braak I-IV NFT co-pathology did not show elevated SUVRs compared to YCs (below mean plus two S.D. threshold calculated from YC SUVRs at each region).

FTP distinguished AD and non-AD primary pathology. CBD could be distinguished from other pathologies. Other non-AD tauopathies and FTLD-TDP/FUS showed low levels of tracer binding that were difficult to distinguish from controls. FTP did not detect Braak I-IV NFT pathology.