Amyloid-beta aggregates (Aβ aggregates)

Amyloid-beta (Aβ) aggregates are pathological protein assemblies formed from the proteolytic cleavage of the amyloid precursor protein (APP) by beta- and gamma-secretases (NIH, 2023). These aggregates exist in a structural continuum ranging from small, soluble oligomers and protofibrils to large, insoluble fibrils that deposit as extracellular senile plaques in the brain parenchyma (PubMed: 30612835). According to the amyloid cascade hypothesis, the accumulation and spreading of these toxic species are primary drivers of Alzheimer's disease pathogenesis, leading to synaptic impairment, neuroinflammation, and eventually neuronal death (PubMed: 29455463). Therapeutic interventions, particularly monoclonal antibodies, target these aggregates to promote their clearance or neutralize their toxicity (PubMed: 36521215). While clearing Aβ aggregates has shown efficacy in slowing cognitive decline in early-stage patients, the management of side effects like amyloid-related imaging abnormalities (ARIA) remains a significant clinical challenge (PubMed: 34103306, PubMed: 37459331).

Other names

Amyloid-beta oligomersAmyloid-beta fibrilsBeta-amyloid aggregatesAβ plaquesAbeta aggregatesAmyloid-beta protofibrils

Monoclonal antibodies target specific conformational epitopes on amyloid-beta aggregates (such as protofibrils or plaques), facilitating their removal from the brain via Fc-receptor-mediated phagocytosis by microglia or by promoting the direct dissolution of existing deposits (PubMed: 36521215, PubMed: 34103306).