In vivo PET classification of tau pathologies in patients with frontotemporal dementia

Frontotemporal dementia (FTD) refers to a group of neurodegenerative disorders with diverse clinical and neuropathological features. In vivo neuropathological assessments of FTD at an individual level have hitherto not been successful. Here, we aimed to classify patients with FTD based on topologies of tau protein aggregates captured by PET with 18F-florzolotau (aka 18F-APN-1607, 18F-PM-PBB3), which allows high-contrast imaging of diverse tau fibrils in Alzheimer’s disease as well as in non-Alzheimer’s disease tauopathies. Twenty-six patients with FTD, 15 with behavioral variant FTD and 11 with other FTD phenotypes, and 20 age- and sex-matched healthy controls were included in this study. They underwent PET imaging of amyloid and tau depositions with 11C-PiB and 18F-florzolotau, respectively. By combining visual and quantitative analyses of PET images, the behavioral variant FTD patients were classified into the following subgroups: 1) predominant tau accumulations in frontotemporal and frontolimbic cortices resembling three-repeat tauopathies (n = three); 2) predominant tau accumulations in posterior cortical and subcortical structures indicative of four-repeat tauopathies (n = four); 3) amyloid and tau accumulations consistent with Alzheimer’s disease (n = four); 4) no overt amyloid and tau pathologies (n = four). Despite these distinctions, clinical symptoms and localizations of brain atrophy did not significantly differ among the identified behavioral variant FTD subgroups. Patients with other FTD phenotypes were also classified into similar subgroups. The results suggest that PET with 18F-florzolotau potentially allows the classification of each individual with FTD on a neuropathological basis, which might not be possible by symptomatic and volumetric assessments.