Baseline CSF tau and short‐term clinical change during lecanemab therapy: A prospective real‐world cohort study in Japan

Abstract INTRODUCTION Real‐world prognostic evidence for cerebrospinal fluid (CSF) biomarkers during lecanemab therapy remains limited. We examined whether baseline CSF phosphorylated tau 181 (pTau181), total tau, and amyloid beta (Aβ) 42/Aβ40 were associated with 6‐month clinical change. METHODS This prospective single‐center cohort included 50 patients with early Alzheimer's disease spectrum treated with lecanemab. CSF biomarkers were measured using the Lumipulse G system. The primary outcome was 6‐month change in Clinical Dementia Rating Sum of Boxes (CDR‐SB). Models were adjusted for age, sex, and baseline Mini‐Mental State Examination; sensitivity analyses included APOE ε4 status. RESULTS CDR‐SB worsening occurred in 19 participants (38.0%). Higher pTau181 (β per SD = 0.408; 95% CI: 0.106 to 0.709; p = 0.0091) and total tau ( β = 0.341; 95% CI: 0.032 to 0.651; p = 0.0314) were associated with worsening. Aβ42/Aβ40 was not. DISCUSSION Baseline CSF pTau181 and total tau were associated with 6‐month clinical trajectories, supporting cautious cohort‐level risk stratification.