Establishing and validating unbiased cut‐offs for tau PET with Gaussian mixture model in Alzheimer’s disease

Background Tau PET positivity (T + ) is recommended in Alzheimer’s disease (AD) trials involving preclinical and prodromal AD. As unbiased cut‐offs are still lacking, we established and validated data‐driven T + PET cut‐offs for AD. Method Data were from ADNI (estimation cohort) and Geneva memory center (validation cohort). 18 F‐Flortaucipir standardized uptake value ratios (SUVr) were computed for a global temporal meta‐ROI and for cortical regions corresponding to Braak‐based stages I‐VI in amyloid negative (Aβ − ) cognitively normal (CN), Aβ + CN, Aβ + MCI and AD. For Tau PET data‐driven cut‐off estimation, Gaussian mixture model (GMM) was applied on the global and regional SUVr distributions in Aβ − CN and AD (n = 269). The GMM cut‐offs’ performance was compared with published 18 F‐Flortaucipir cut‐offs (Mattsson et al., 2017) by assessing the percentage of T + subjects within each diagnostic group. Result Cut‐offs were 1.36 for temporal meta‐ROI and ranged 1.20‐1.39 for stages. In the validation cohort, all Aβ − CN were tau negative (T − ), while T + percentage increased along the Aβ + continuum (CN