Fig. 2

Amyloid aggregation in AD and the mechanism of action of gantenerumab. A The amyloid hypothesis of AD involves the accumulation of Aβ-soluble monomers and oligomers that aggregate into insoluble fibrils and amyloid plaques. Aggregated species of Aβ damages neurons and can increase oxidative stress, inflammation, mitochondrial dysfunction, and neuronal loss. B Based on the findings from in vitro studies, the mechanism of action of gantenerumab is thought to stem from the clearance of Aβ plaques by antibody-induced cell-mediated phagocytosis, dissociation of Aβ peptide aggregates by direct resolution, and neutralization of neurotoxic Aβ oligomers. Gantenerumab binds to all types of aggregated neurotoxic Aβ species, with the highest affinity to the fibrillar forms and plaques. After binding to aggregated amyloid (1), the Fc gamma receptor on microglia binds to the human immunoglobulin G1 backbone of gantenerumab, engulfing Aβ plaques (2), and, then, phagocytosis by microglia and removal of aggregated Aβ (3). A Adapted with permission from Panza F, et al. Nat Rev Neurol. 2019;15(2):73-88