Lecanemab, sold under the name Leqembi, is a monoclonal antibody therapy for Alzheimer’s disease that clears toxic amyloid plaques and delays cognitive decline. Researchers from VIB and KU Leuven have now demonstrated the mechanism behind it for the first time.
They showed that the “Fc fragment” of this monoclonal antibody is essential for engaging microglia—the immune cells of the brain—thus initiating the cellular machinery needed for plaque removal. This is the first direct mechanistic explanation for how this class of therapies works. It clarifies uncertainties in the field and offers a blueprint for developing safer, more effective Alzheimer’s treatments. The findings are published in Nature Neuroscience.
“Our study is the first to clearly demonstrate how this anti-amyloid antibody therapy works in Alzheimer’s disease. We show that the therapy’s efficacy relies on the antibody’s Fc fragment, which activates microglia to effectively clear amyloid plaques,” says Dr. Giulia Albertini, co-first author of the study. “The Fc fragment works as an anchor that microglia latch onto when they are near plaques, as a consequence of which these cells are reprogrammed to clear plaques more efficiently.”
