Comparative assessment of regional tau distribution by Tau-PET and Post-mortem neuropathology in a representative set of Alzheimer’s & frontotemporal lobar degeneration patients

Abstract

Flortaucipir (FTP) PET is a key imaging technique to evaluate tau burden indirectly. However, it appears to have greater utility for 3R+4R tau found in Alzheimer’s disease (AD), compared to other non-AD tauopathies. The purpose of this study is to determine how flortaucipir uptake links to neuropathologically determined tau burden in AD and non-AD tauopathies. We identified nine individuals who had undergone antemortem tau-PET and postmortem neuropathological analyses. The cohort included three patients with low, moderate, and high AD neuropathologic changes (ADNC), five patients with a non-AD tauopathy (one Pick’s disease, three progressive supranuclear palsies, and one globular glial tauopathy), and one control without ADNC. We compared regional flortaucipir PET uptake with tau burden using an anti-AT8 antibody. There was a very good correlation between flortaucipir uptake and tau burden in those with ADNC although, in one ADNC patient, flortaucipir uptake and tau burden did not match due to the presence of argyrophilic grains disease. Non-AD patients showed lower flortaucipir uptake globally compared to ADNC patients. In the non-AD patients, some regional associations between flortaucipir uptake and histopathological tau burden were observed. Flortaucipir uptake is strongly linked to underlying tau burden in patients with ADNC but there are instances where they do not match. On-the-other hand, flortaucipir has a limited capacity to represent histopathological tau burden in non-AD patients although there are instances where regional uptake correlates with regional tau burden. There is a definite need for the development of future generations of tau-PET ligands that can detect non-AD tau.