Lecanemab preferentially binds to smaller aggregates present at early Alzheimer's disease.

ABSTRACT:

Introduction

The monoclonal antibodies Aducanumab, Lecanemab, Gantenerumab, and Donanemab were developed for the treatment of Alzheimer's disease (AD).

Methods

We used single-molecule detection and super-resolution imaging to characterize the binding of these antibodies to diffusible amyloid beta (Aβ) aggregates generated in-vitro and harvested from human brains.

Results

Lecanemab showed the best performance in terms of binding to the small-diffusible Aβ aggregates, affinity, aggregate coating, and the ability to bind to post-translationally modified species, providing an explanation for its therapeutic success. We observed a Braak stage-dependent increase in small-diffusible aggregate quantity and size, which was detectable with Aducanumab and Gantenerumab, but not L

SUBMITTER: Fertan E 

PROVIDER: S-EPMC12001052 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature