IN VIVO CLASSIFICATION OF TAU PATHOLOGIES BY POSITRON EMISSION TOMOGRAPHY IN PATIENTS WITH FRONTOTEMPORAL DEMENTIA

Abstract Background Frontotemporal dementia (FTD) is a group of neurodegenerative disorders with diverse clinical and neuropathological features. In vivo neuropathological assessments of FTD at an individual level have not hitherto been successful. Aims & Objectives In this study, we aimed to classify patients with FTD based on topologies of tau protein aggregates captured by positron emission tomography (PET) with 18F-florzolotau (aka 18F-APN-1607, 18F-PM-PBB3), which allows high-contrast imaging of diverse tau fibrils in Alzheimer’ s disease (AD) and non-AD tauopathies. Method Twenty-six patients with FTD, consisting of 15 patients with behavioral variant FTD (bvFTD) and 11 patients with other FTD phenotypes, and 20 age- and gender-matched healthy controls were studied. They underwent PET imaging of amyloid and tau depositions with 11C-PiB and 18F-florzolotau, respectively. Results By combining visual and semiquantitative analyses of PET images, the bvFTD patients were classified into the following subgroups: 1) predominant tau accumulations in frontotemporal and frontolimbic cortices resembling three-repeat tauopathies (n = 3); 2) predominant tau accumulations in subcortical structures accompanied by various degrees of neocortical accumulations resembling four-repeat tauopathies (n = 4); 3) amyloid and tau accumulations consistent with AD (n = 4); and 4) no overt amyloid and tau pathologies (n = 4). Despite these distinctions, clinical symptoms and localization of brain atrophy were not significantly different among the identified bvFTD subgroups. Patients with other FTD phenotypes were also classified into similar subgroups. Discussion And Conclusion PET with 18F-florzolotau potentially enables the characterization of each individual with FTD on a biological basis, thereby possibly contributing to diagnostic and therapeutic approaches to this illness.