Anti-amyloid-β (Aβ) monoclonal antibodies are designed to selectively target protein biomarkers and promote amyloid clearance in Alzheimer’s disease. Yet the effects of antibodies on individual Aβ protein aggregates remain to be fully clarified. The work presented here employs nanospectroscopy (atomic force microscopy combined with infrared spectroscopy) to resolve morphological and secondary structural changes in Aβ-42 protein aggregates upon treatment with aducanumab and lecanemab antibodies (biosimilars). The treatment of Aβ-42 peptides with aducanumab resulted in reduction of oligomer prevalence and formation of larger-diameter fibril bundles confirmed from the AFM height maps and infrared spectral readouts recorded at nanometer-scale spatial resolution. Conversely, lecanemab treatment of Aβ-42 peptides did not suppress oligomer generation but was observed to preferentially bind along the full length of the nodular-shaped protofibril surface. Importantly, neither aducanumab nor lecanemab was observed to induce any surface adsorption-driven disassembly of Aβ-42 protofibrils or elongated mature fibrils. Thus, nanospectroscopy enables direct characterization of antibody–amyloid interfacial interactions and provides insights into the distinct modes of action of emerging anti-Aβ therapeutics through label-free chemical imaging.
Kummer et al. (Thu,) studied this question.