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

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.

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.

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.

Baseline CSF pTau181 and total tau were associated with 6-month clinical trajectories, supporting cautious cohort-level risk stratification.
Mental Health
Care/Management

Authors

Takahashi Takahashi, Kashibayashi Kashibayashi, Fujita Fujita, Yoshida Yoshida, Hashiramoto Hashiramoto, Kowa Kowa, Mizuta Mizuta
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