[18F]Flortaucipir PET to autopsy pathology comparisons in Alzheimer's disease and other neurodegenerative diseases: Biomarkers: Leveraging postmortem collections to validate neuroimaging. (7th December 2020) - Soleimani‐Meigooni, David N.
Abstract: Background: Few studies have evaluated the relationship between in vivo [ 18 F]Flortaucipir (FTP) PET and post‐mortem pathology. Method: We sought to compare antemortem FTP‐PET to neuropathology in a consecutive series of patients with a broad spectrum of neurodegenerative diseases. 80‐100 min FTP‐PET standardized uptake value ratio (SUVR) images were created using an inferior cerebellar gray matter reference. W‐score maps were generated to highlight areas of increased tracer retention compared to cognitively normal controls, adjusting for age as a covariate. Autopsies were performed blinded to PET results. Mean SUVRs were calculated for Braak stage regions of interest (ROIs), and these values were compared to SUVRs derived from young, non‐autopsy, cognitively normal controls used as a standard for tau negativity. Result: Nineteen patients were included (mean age at PET 61 [range 34‐76]; 8 female; mean PET‐to‐autopsy time of 30 months [range 4‐59 months]; Table 1). Eight patients had primary Alzheimer's disease (AD) pathology, 9 had non‐AD tauopathies (progressive supranuclear palsy [PSP], corticobasal degeneration [CBD], argyrophilic grain disease [AGD], and frontotemporal lobar degeneration [FTLD] with tau inclusions), 2 patients had non‐tau related FTLD. There was excellent correspondence between areas of FTP retention and neurofibrillary tangle (NFT) distribution in patients with primary AD neuropathology. Patients with non‐AD tauopathies showed a range of tracer retention that was less than AD and more than age‐matched, cognitively normal controls, with CBD and FTLD due to MAPT mutations showing the most extensive and distinct binding patterns (Figure 1). Patients with non‐tau related FTLD also showed small areas of tracer retention (Figure 1). Overall, binding across both tau‐positive and tau‐negative non‐AD disorders did not reliably correspond with post‐mortem tau pathology. Quantification of FTP‐PET SUVR images at Braak stage ROIs reliably detected high Alzheimer's Disease Neuropathologic Change (Braak VI) pathology. However, patients with earlier Braak stages did not show elevated tracer uptake in these regions compared to young, tau‐negative controls (Figure 2). Conclusion: In summary, PET‐to‐autopsy correlations confirm that FTP‐PET is a reliable biomarker of advanced tau pathology in AD. The tracer cannot reliably differentiate non‐AD tauopathies and may not detect early Braak stages of NFT pathology.