Unsupervised [(18)F]Flortaucipir cutoffs for tau positivity and staging in Alzheimer’s disease

PURPOSE: Several [(18)F]Flortaucipir cutoffs have been proposed for tau PET positivity (T(+)) in Alzheimer’s disease (AD), but none were data-driven. The aim of this study was to establish and validate unsupervised T(+) cutoffs by applying Gaussian mixture models (GMM). METHODS: Amyloid negative (A(−)) cognitively normal (CN) and amyloid positive (A(+)) AD-related dementia (ADRD) subjects from ADNI (n=269) were included. ADNI (n=475) and Geneva Memory Clinic (GMC) cohorts (n=98) were used for validation. GMM-based cutoffs were extracted for the temporal meta-ROI, and validated against previously published cutoffs and visual rating. RESULTS: GMM-based cutoffs classified less subjects as T(+), mainly in the A(−) CN (<3.4% vs >28.5%) and A(+) CN (<14.5% vs >42.9%) groups and showed higher agreement with visual rating (ICC=0.91 vs ICC<0.62) than published cutoffs. CONCLUSION: We provided reliable data-driven [(18)F]Flortaucipir cutoffs for in vivo T(+) detection in AD. These cutoffs might be useful to select participants in clinical and research studies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00259-023-06280-7.