Higher phosphorylated tau levels predict cognitive decline and amyloid-related imaging abnormalities during lecanemab...

Lecanemab was recently approved for the treatment of patients with early Alzheimer's disease (AD) and demonstrated reduced senile amyloid plaque and less decline on the measures of cognition and function in clinical trials. However, the real-world data on its efficacy and safety remain limited. We aimed to evaluate the effectiveness and tolerance of lecanemab treatment and determine biomarkers at baseline that could predict cognitive deterioration and the occurrence of amyloid-related imaging abnormaities (ARIA) in real-world clinical practice.

To determine the indication for lecanemab, the patients were evaluated through neurological examinations, cognitive assessments, blood test, head magnetic resonance imaging (MRI), amyloid positron emission tomography, lumbar puncture, genetic testing, and clinical conferences. The Mini-Mental State Examination (MMSE) was used to assess cognition, and the MRI scans were used for safety monitoring of ARIA.

Between January 2024 and October 2025, 234 patients were screened, 100 initiated lecanemab treatment. The mean age was 72.7 years, and 68 (68.0%) patients were female. Among the 71 patients surveyed via MRI prior to the 14th infusion, 12 (16.9%) had ARIA detected. Compared with those of patients without ARIA, the baseline cerebrospinal fluid (CSF)-ptau181 levels of patients with ARIA significantly increased. When the patients were divided into high and low CSF-ptau181 groups according to the cutoff value (78.6 pg/ml) which derived from ROC analysis for ARIA prediction, the MMSE scores of the high ptau group were significantly declined compared to that of the low ptau group at 6 and 12 months after baseline. The infusion-reactions occurred only in 6.0% of patients. The longitudinal observation revealed that the plasma thrombomodulin levels significantly decreased after 6 months of lecanemab treatment.

Lecanemab was generally well tolerated by most patients with early AD and treatment appeared to be more effective and safer in patients with low CSF-ptau181 levels.　Our results suggest an association between lecanemab treatment and reduced markers of vascular endothelial injury.