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

Alzheimer's & dementia : the journal of the Alzheimer's Association

Authors: Jesús Silva-Rodríguez, Linda Zhang, Luca Kleineidam, Francisco J López-González, Sonia Wagner-Reguero, Minerva Martínez-Castillo, Aitana Sogorb-Esteve, Michelle E Guamán-Chulunchana, Ana B Pastor, Nekane Moreno, Andrea Ruiz-Calvo, Cristina Sánchez-Martín, Eva Alfayate, Marta Molero-Cartón, Elizabeth L Valeriano-Lorenzo, Belén Frades-Payo, Meritxell Valentí, María A Zea-Sevilla, Alexis Moscoso, Alfredo Ramírez, Pamela Martino-Adami, Steffi G Riedel-Heller, Martin Scherer, Andreas Jeromin, Miguel Calero, Teodoro Del Ser, Anja Schneider, Michel J Grothe, Pascual Sánchez-Juan

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.

© 2026 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

PMID: 42483984

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