Amyloid-beta (Aβ) aggregate (Aβ)

Amyloid-beta (Aβ) aggregates, primarily composed of Aβ42 peptides, are a hallmark pathological feature of Alzheimer's disease [National Institute on Aging]. These aggregates form extracellular plaques in the brain parenchyma, leading to neuroinflammation, synaptic loss, and eventual neuronal death [StatPearls]. The 'amyloid cascade hypothesis' suggests that the accumulation of these fibrils is a primary driver of the disease's progression [Hardy & Higgins, Science 1992]. Therapeutic strategies focus on reducing the plaque burden through monoclonal antibodies that target various forms of the aggregated protein, including protofibrils and insoluble plaques [FDA]. Clinical trials for drugs like lecanemab and donanemab have shown that clearing these aggregates can slow cognitive decline in early-stage patients, though the treatment is associated with risks like Amyloid-Related Imaging Abnormalities (ARIA) [van Dyck et al., NEJM 2023; Sperling et al., Alzheimer's & Dementia 2011].

Other names

Beta-amyloid plaquesAggregated Aβ fibrilsSenile plaquesNeuritic plaquesAmyloid-beta fibrilsCerebral beta-amyloid plaques

Monoclonal antibodies bind to specific epitopes on aggregated amyloid-beta (fibrils or plaques), facilitating their clearance by microglia via Fc-mediated phagocytosis or preventing further deposition [FDA; van Dyck et al., NEJM 2023].