Heterogeneity in plasma p‐tau217 response and its association with cognitive trajectories under lecanemab treatment
Sung Hoon Kang, Yu Jeong Park, Seungyun Lee, Jimin Kang, Seongin Lee, Eun Seong Lee, Hye Na Jung, Inseon Ryoo, Hyundoo Hwang, Kwangho Choi, Jae Seon Eo, Sang‐Il Suh, Kyungmi Oh, Seong‐Beom KohAbstract
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.