Amyloid-beta (Aβ) protein aggregate (Aβ aggregate)

Amyloid-beta (Aβ) aggregates are misfolded protein assemblies derived from the proteolytic cleavage of the amyloid precursor protein (APP) by beta- and gamma-secretases (UniProt P05067). These aggregates exist in a continuum of states, including soluble oligomers, protofibrils, and insoluble fibrils that deposit as extracellular senile plaques in the brain parenchyma (PubMed: 30612835). The accumulation of Aβ aggregates is a central hallmark of Alzheimer's disease pathogenesis, where they are thought to trigger a cascade of neurotoxic events, including synaptic dysfunction, neuroinflammation, and the induction of tau pathology (Alzheimer's Association). Therapeutic strategies primarily focus on enhancing the clearance of these aggregates from the brain using monoclonal antibodies (FDA). Recent clinical successes with drugs like lecanemab and donanemab have validated Aβ aggregates as a viable therapeutic target for slowing cognitive decline in early-stage Alzheimer's patients (NEJM: 3640350). However, targeting these aggregates is associated with specific safety risks, most notably amyloid-related imaging abnormalities (ARIA), which require careful monitoring via MRI (PubMed: 33536220).

Other names

Amyloid-beta fibrilsAmyloid-beta oligomersAβ42 aggregatesSenile plaquesAbeta aggregatesAmyloid-beta protofibrils

Monoclonal antibodies target specific conformational epitopes on amyloid-beta aggregates to facilitate their clearance via microglial phagocytosis or to neutralize soluble toxic oligomers (PubMed: 30612835).