Progress in the Study of the Pathogenesis of AD and Its Treatment Based on Lecanemab

Jiaxin He

doi:10.54254/2753-8818/2025.AU25014

Theoretical and Natural ScienceOpen access

Progress in the Study of the Pathogenesis of AD and Its Treatment Based on Lecanemab

Research Article

Open Access

Progress in the Study of the Pathogenesis of AD and Its Treatment Based on Lecanemab

Jiaxin He ^1*

¹ Department of Biotechnology, East China University of Science and Technology, Shanghai, China

^*Corresponding author: 22012351@mail.ecust.edu.cn

Published on 20 July 2025

TNS Vol.126

ISSN (Print): 2753-8826

ISSN (Online): 2753-8818

ISBN (Print): 978-1-80590-265-2

ISBN (Online): 978-1-80590-266-9

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Abstract

Alzheimer's disease (AD), the world's premier neurodegenerative disease, has long lacked effective disease-modifying therapies for its core pathological mechanisms - β-amyloid (Aβ) deposition and tau protein tangles. In recent years, research breakthroughs have focused on anti-Aβ monoclonal antibodies, among which Lecanemab has become the first disease-modifying drug fully approved by the FDA by targeting soluble Aβ protofibrils, with a significant delay in cognitive decline of 27% (CDR-SB) and a manageable risk of ARIA (11.6%) in Phase III. However, the lack of dynamic monitoring technology, the uncertainty of long-term safety, and the cost-effectiveness paradox remain unresolved. This paper systematically analyses Lecanemab's mechanism of action (selective removal of protofibrils), clinical evidence (dose-response and safety in phase II/III trials), and integrate a biomarker (p-tau217) driven stratification strategy with the ARIA risk management framework. It was found that precision interventions for toxic Aβ subtypes can reshape treatment regimens, but need to be combined with tau-targeted therapies to enhance late-stage efficacy. This review provides three major references for precision therapy in AD: establishing the stratification value of early biomarkers, optimising risk-benefit assessment models, and revealing pathways for combination therapy potentiation. In the future, plasma protofibril detection technology needs to be developed, APOE genotype-oriented ARIA prediction algorithms need to be established, and low-cost delivery systems need to be explored to enhance accessibility.

Keywords:

Alzheimer's disease, Lecanemab, β-amyloid protofibrils, Biomarker stratification, ARIA risk management.

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