Comparison of four monoclonal antibodies that bind to amyloid-β (Aβ) in a recent study has demonstrated that lecanemab most effectively binds to small Aβ aggregates that form in the early stages of Alzheimer disease (AD). Fertan et al. used super-resolution microscopy and single-molecule array analysis to study binding of aducanumab, lecanemab, gantenerumab and donanemab to Aβ. Lecanemab preferentially bound to small, diffusable Aβ aggregates, which are present early in AD and are thought to be the main toxic species. This preferential binding could explain why lecanemab has greater clinical benefits than aducanumab and gantenerumab in early AD. However, the clinical effects of donanemab are comparable to those of lecanemab without this preferential binding, suggesting that an alternative mechanism underlies its benefits.