Amyloid-beta peptide aggregates (Aβ aggregates) (Aβ)

Amyloid-beta (Aβ) aggregates are insoluble protein assemblies formed from the misfolding of Aβ monomers, which are proteolytic cleavage products of the amyloid precursor protein (APP) (UniProt: P05067). These aggregates, ranging from small soluble oligomers to large insoluble fibrils and plaques, are a hallmark of Alzheimer's disease pathology (NIH: Alzheimer's Disease Fact Sheet). In the brain, Aβ accumulation is thought to trigger a cascade of neurotoxic events, including synaptic dysfunction, neuroinflammation, and the formation of tau tangles, ultimately leading to neuronal death (PubMed: PMID 30612631). Therapeutic strategies targeting Aβ aggregates primarily involve monoclonal antibodies designed to recognize and bind specific conformations of the peptide, such as protofibrils or mature plaques (PubMed: PMID 36630463). These drugs, including lecanemab and donanemab, aim to reduce the plaque burden by stimulating microglial clearance or inhibiting the recruitment of monomers into existing fibrils (PubMed: PMID 37459977). While several Aβ-targeting therapies have received regulatory approval, they are associated with specific safety risks, most notably amyloid-related imaging abnormalities (ARIA) (FDA: Leqembi Prescribing Information).

Other names

Beta-amyloidA-betaAmyloid-beta fibrilsAmyloid-beta plaquesAβ42Aβ40Senile plaquesAmyloid-beta oligomers

Passive immunization using monoclonal antibodies that target specific aggregated forms of amyloid-beta (such as protofibrils or plaques) to promote their clearance via microglial phagocytosis or to inhibit further fibril elongation (PubMed: PMID 36630463).