Longitudinal plasma phosphorylated tau217 classification and the association with Alzheimer's disease progression

INTRODUCTION Longitudinal diagnostic and prognostic validity of plasma phosphorylated tau217 (p‐tau217) in Alzheimer's disease (AD) remains uncertain. METHODS In this multi‐cohort study of 2117 individuals, we established baseline plasma p‐tau217 thresholds for amyloid‐β–positron emission tomography (Aβ‐PET) and assessed their longitudinal classification stability and prognostic relevance for AD‐related outcomes. RESULTS Baseline‐defined cutoffs achieved high and sustained accuracy (86%–95%) for Aβ‐PET positivity over up to 5 years of follow‐up. Longitudinally, most p‐tau217–positive individuals remained stable (93%–98%), whereas the intermediate zone group progressed more to positive (44%–78%) than p‐tau217–negative individuals (4%–21%). Participants with stable‐positive and progress‐to‐positive p‐tau217 profiles more frequently exhibited Aβ abnormalities (90%–100% and 64%–96%, respectively) and experienced accelerated tau accumulation, hippocampal atrophy, and incident dementia compared to those with a stable‐negative p‐tau217 profile. DISCUSSION These findings support the high stability and Aβ‐PET classification performance of longitudinal plasma p‐tau217 monitoring in AD, providing a scalable tool for risk stratification and disease monitoring.