Heterogeneity in plasma p-tau217 response and its association with cognitive trajectories under lecanemab treatment.

INTRODUCTION

Plasma phosphorylated tau 217 (p-tau217) is a promising biomarker for monitoring treatment response in Alzheimer's disease (AD), but its longitudinal dynamics and clinical relevance remain unclear.

METHODS

In this prospective real-world study, 153 patients with early AD receiving lecanemab were analyzed. Longitudinal changes in plasma p-tau217 were assessed, and trajectory patterns were identified using clustering and slope-based approaches. Associations with baseline factors and cognitive outcomes were evaluated.

RESULTS

Plasma p-tau217 levels decreased significantly from 3 months, with the greatest decline between 3 and 6 months, followed by a plateau. Two distinct trajectory groups were identified. Patients in the greater reduction group showed more favorable cognitive trajectories, particularly slower progression in Clinical Dementia Rating-Sum of Boxes (CDR-SB) scores. Hypertension was associated with a diminished biomarker response.

DISCUSSION: These findings support plasma p-tau217 as an early pharmacodynamic biomarker and highlight its potential role in guiding individualized treatment strategies in routine clinical practice.