Anti-amyloid antibody therapies for Alzheimer's disease: how much do we really understand?

A new study published in Nature Neuroscience demonstrated that Fc effector function is essential for amyloid aggregate clearance during lecanemab treatment, a recently FDA-approved therapy for Alzheimer's disease. These findings underscore the requirement for intact Fc-mediated activity to achieve therapeutic efficacy. In addition, single-cell RNA sequencing identified microglia transcriptomic changes that are unique to lecanemab treatment and extend beyond previously characterized microglial activation signatures. Together with a retrospective review of anti-amyloid antibody development and related mechanisms, this commentary provides important insights into new directions for the design of next-generation therapies for Alzheimer's disease.