Amyloid-beta 42 oligomer and aggregate (Aβ42)

Amyloid-beta 42 (Aβ42) oligomers and aggregates are pathological assemblies of the 42-amino acid peptide produced by the cleavage of amyloid precursor protein (APP) (UniProt: P05067). These species, particularly soluble oligomers and protofibrils, are considered the primary neurotoxic agents in Alzheimer's disease, leading to synaptic loss and neuronal death (PubMed: 27582220). Aβ42 has a higher propensity to aggregate than the more abundant Aβ40 isoform, forming the core of neuritic plaques found in the brains of affected individuals (NIH: National Institute on Aging). The aggregation process involves the transition from monomers to soluble oligomers, then to insoluble fibrils and plaques. Therapeutic interventions, such as the FDA-approved monoclonal antibodies lecanemab and aducanumab, specifically target these aggregated forms to promote their clearance via microglial-mediated phagocytosis (PubMed: 36630468). These drugs aim to slow cognitive decline by reducing the burden of toxic amyloid species in the brain. While effective at reducing plaque burden, these therapies are associated with amyloid-related imaging abnormalities (ARIA), necessitating careful patient monitoring (StatPearls: Alzheimer Disease). Monitoring often involves amyloid PET imaging or measuring Aβ42 levels in cerebrospinal fluid or plasma.

Other names

Amyloid-beta 1-42Abeta42Aβ42 protofibrilsAmyloid-beta peptide 42Soluble Aβ42 oligomers

Monoclonal antibodies bind to specific epitopes on Aβ42 oligomers, protofibrils, or insoluble plaques to facilitate their clearance via microglial phagocytosis or to neutralize their neurotoxic effects (PubMed: 36630468, 27582220).