Amyloid-beta peptide 1-42 (Aβ42) (Aβ42)

Amyloid-beta peptide 1-42 (Aβ42) is a 42-amino acid peptide derived from the proteolytic cleavage of the amyloid precursor protein (APP) by beta- and gamma-secretases (PubMed: 28453508). While Aβ42 may play roles in synaptic plasticity and antimicrobial defense at physiological concentrations, its propensity to aggregate into neurotoxic oligomers and insoluble extracellular plaques is a hallmark of Alzheimer's disease (UniProt: P05067). The burden of Aβ42 refers to the cumulative accumulation of these aggregates, which are thought to trigger a cascade of neuroinflammation, tau hyperphosphorylation, and synaptic loss (NIH: Alzheimer's Disease Fact Sheet). Therapeutic interventions primarily focus on reducing this burden through monoclonal antibodies that promote microglial clearance of plaques or by inhibiting the enzymes responsible for its production (StatPearls: NBK499922). Clinical success with drugs like lecanemab and donanemab has validated Aβ42 as a central therapeutic target, although treatment is often associated with safety risks such as amyloid-related imaging abnormalities (ARIA) (PubMed: 36599384). Monitoring Aβ42 levels in cerebrospinal fluid or via PET imaging is essential for diagnosis and evaluating treatment efficacy in clinical settings (PubMed: 30107561).

Other names

Amyloid-beta 1-42Abeta 42Aβ1-42Amyloid beta-peptide 42Beta-amyloid 42Aβ42 burden

Monoclonal antibodies target and facilitate the clearance of Aβ42 protofibrils, oligomers, or insoluble plaques from the brain via microglial phagocytosis. Other strategies include BACE1 inhibition to prevent the cleavage of amyloid precursor protein (APP) into Aβ42.