Amyloid-beta peptide protofibrils (Aβ protofibrils)

Amyloid-beta (Aβ) peptide protofibrils are soluble, intermediate-stage aggregates of the Aβ peptide, typically ranging in size from 75 to 500 kDa (Söderberg et al., 2023). They are formed during the transition from small, low-molecular-weight oligomers to large, insoluble fibrils that constitute amyloid plaques in the brains of patients with Alzheimer's disease (Walsh et al., 1997). Protofibrils are considered highly neurotoxic, contributing to synaptic loss, neuroinflammation, and neuronal death (Lannfelt et al., 2014). Unlike insoluble plaques, protofibrils are soluble and can diffuse through the brain parenchyma, exerting widespread toxic effects (Sehlin et al., 2019). Therapeutic strategies, most notably the monoclonal antibody lecanemab, specifically target these protofibrils to reduce their concentration and slow cognitive decline in early-stage Alzheimer's disease (van Dyck et al., 2023). By binding to these species, drugs promote their clearance via microglial phagocytosis and disrupt the amyloid cascade before the formation of extensive plaque deposits (Swanson et al., 2021).

Other names

Soluble amyloid-beta protofibrilsAbeta protofibrilsAβ soluble aggregatesAmyloid-beta oligomers (large)

Monoclonal antibodies bind selectively to soluble amyloid-beta protofibrils, facilitating their clearance via microglia-mediated phagocytosis and preventing their further maturation into insoluble fibrils and plaques (Söderberg et al., 2023; van Dyck et al., 2023).