Uptake of tau-PET and neuropathological and autoradiographic findings from a globular glial tauopathy case series.

INTRODUCTION: Globular glial tauopathy (GGT) is a rare type of frontotemporal lobar degeneration (FTLD) characterized by deposition of 4-repeat tau. Detecting GGT with tau positron emission tomography (tau-PET) is challenging. We aim to determine the associations between tau-PET, autoradiography, and neuropathology methods in GGT. METHODS: We identified three patients with GGT who had completed antemortem tau-PET. Healthy control and two patients with Alzheimer's disease (AD) were also included for comparison. We analyzed gray matter (GM) and white matter (WM) from the superior/middle frontal gyrus (S/M-FG) and the superior/middle temporal gyrus (S/M-TG). Immunohistochemical staining was performed with antibodies against phospho-tau (AT8, PHF-1, RD4), glial fibrillary acidic protein (GFAP), and resting microglia (ionized calcium-binding adaptor molecule 1; Iba1). Immunofluorescence with a fluorescent tau-PET analog (T726) was performed. Regional tau-PET standardized uptake value ratios (SUVRs) were calculated for comparative GM and WM regions. Autoradiographic studies with 18F-AV1451 were also conducted. RESULTS: Tau-PET showed increased uptake in the WM regions of the S/M-FG and S/M-TG in GGT, and the GM regions in AD. Co-localization was observed between T726 and PHF-1, RD4, and GFAP in the WM in the patients with GGT, whereas co-localization was observed with PHF-1 predominantly in the GM in AD. Little co-localization was observed with Iba1. In vitro 18F-AV1451 autoradiography studies demonstrated minimal binding in GGT. Tau-PET differentiated underlying GGT from AD based on the relative involvement of the WM and GM. CONCLUSION: Histopathologic findings suggest that some flortaucipir uptake in GGT may represent underlying 4R tau, whereas autoradiographic analysis suggests that uptake is likely due to off-target binding. Further studies with larger cohorts are needed to determine the pathological basis of flortaucipir uptake in GGT.