Prognostic value of plasma %p‐tau217 in cognitively unimpaired older adults

INTRODUCTION: We evaluated the prognostic value of baseline plasma phosphorylated tau 217 ratio (%p-tau217) for predicting long-term progression in cognitively unimpaired (CU) older adults. METHODS: We analyzed 982 community-dwelling individuals followed annually for up to 12 years. Baseline %p-tau217 levels were quantified by mass spectrometry and stratified into four strata using previously defined cut-offs. Outcomes included longitudinal changes in cognition, neurodegeneration, and progression to mild cognitive impairment (MCI)/dementia. Results were replicated with immunoassays in the same and an independent primary care cohort (n = 1204). RESULTS: Participants with Elevated/High %p-tau217 exhibited accelerated cognitive decline, hippocampal atrophy, and significantly higher risks of progression to MCI (hazard ratio [HR] > 6.0) and dementia (HR > 9.9). The Low group demonstrated a 92.2% 10-year negative predictive value for any progression. DISCUSSION: Our results suggest that %p-tau217 is a robust prognostic biomarker, accurately distinguishing CU individuals at minimal risk from those at high risk of future AD-related clinical and neurodegenerative decline. Similar performance was achieved by immunoassays.