What the Gantenerumab Trials Teach Us about Alzheimer’s Treatment

An amyloid hypothesis1 for Alzheimer’s disease posits that amyloid-beta (Aβ) peptides cleaved from Aβ precursor protein trigger a neurodegenerative cascade, causing cognitive and functional impairment. The peptides have various lengths, ranging from monomers to self-assembled soluble oligomers, insoluble fibrils, and extracellular deposits, or plaques. Any of these species could be toxic. The antiamyloid monoclonal antibodies aducanumab2 and lecanemab3 have been approved by the Food and Drug Administration (FDA) for the treatment of early Alzheimer’s disease; donanemab4 seems to be headed for approval. Aducanumab and lecanemab received accelerated approval on the basis of a reduction in amyloid plaques. Lecanemab later received . . .