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.