Single-molecule characterisation of soluble beta-amyloid aggregate binding by Aducanumab, Lecanemab, Gantenerumab, and Donanemab
Emre Fertan, Jeff Y. L. Lam, Giulia Albertini, Maarten Dewilde, Yunzhao Wu, Oluwatomi E. S. Akingbade, Dorothea Böken, Elizabeth A. English, Bart De Strooper, David A. Klenerman · bioRxiv (Cold Spring Harbor Laboratory) · 2024
Abstract Monoclonal antibodies Aducanumab, Lecanemab, Gantenerumab, and Donanemab have been developed for treatment of Alzheimer’s disease. Here, we have used single-molecule detection techniques and super-resolution imaging to characterise the binding of these antibodies to beta-amyloid aggregates including human post-mortem brain samples. Lecanemab is the best antibody in terms of binding to the small-soluble beta-amyloid aggregates, affinity, aggregate coating, and the ability to bind to post-translationally modified species, explaining its therapeutic success.