Single-molecule characterisation of soluble beta-amyloid aggregate binding by Aducanumab, Lecanemab, Gantenerumab, and Donanemab
Emre FertaniD, Jeff Y. L. LamiD, Giulia AlbertiniiD, Maarten DewildeiD, Yunzhao WuiD, Oluwatomi E. S. AkingbadeiD, Dorothea BökeniD, Elizabeth A. English, Bart De StrooperiD, David KlenermaniD
Abstract
Monoclonal antibodies Aducanumab, Lecanemab, Gantenerumab, and Donanemab have been developed for treatment of Alzheimers 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.
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