Amyloid-beta protein 42 (Abeta42) (Abeta42)

Amyloid-beta protein 42 (Abeta42) is a 42-amino acid peptide resulting from the proteolytic cleavage of the amyloid precursor protein (APP) by the enzymes beta-secretase and gamma-secretase (UniProt: P05067). It is a key pathological hallmark of Alzheimer's disease, where it aggregates into soluble oligomers, protofibrils, and insoluble neuritic plaques within the brain parenchyma (PubMed: 11959137). Abeta42 is distinguished from the more common Abeta40 isoform by its higher hydrophobicity and faster rate of aggregation, making it significantly more neurotoxic and central to the 'amyloid cascade' theory of neurodegeneration (PubMed: 28263302). Therapeutically, Abeta42 is the primary target for several monoclonal antibodies, such as lecanemab and donanemab, which are designed to reduce brain amyloid burden and slow cognitive decline in early-stage Alzheimer's patients. Clinically, monitoring Abeta42 levels in cerebrospinal fluid or via positron emission tomography (PET) is essential for diagnosis and evaluating treatment efficacy (PubMed: 30107350).

Other names

Amyloid beta-peptide 1-42Beta-amyloid 42Abeta 1-42Abeta-42A-beta-42

Monoclonal antibodies target specific conformations of Amyloid-beta protein 42, including soluble oligomers, protofibrils, or insoluble fibrils, to trigger microglial-mediated phagocytosis and clearance from the brain or to neutralize toxic species and prevent further plaque deposition.