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Single-molecule characterisation of soluble beta-amyloid aggregate binding by Aducanumab, Lecanemab, Gantenerumab, and Donanemab

Fertan, E.; Lam, J. Y. L.; Albertini, G.; Dewilde, M.; Wu, Y.; Akingbade, O. E. S.; Boeken, D.; English, E. A.; De Strooper, B.; Klenerman, D.

2024-10-12 neuroscience
10.1101/2024.10.11.617910 bioRxiv
Show 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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