Amyloid-beta 42 (Aβ42) (Aβ42)

Amyloid-beta 42 (Aβ42) is a 42-amino acid peptide generated from the proteolytic cleavage of the amyloid precursor protein (APP) by the enzymes beta-secretase and gamma-secretase (UniProt P05067). In its monomeric state, Aβ42 is a soluble, intrinsically disordered protein that is believed to play physiological roles in modulating synaptic plasticity, memory formation, and providing antimicrobial defense at low concentrations (PubMed 29033854). However, the Aβ42 monomer is highly amyloidogenic and serves as the primary building block for neurotoxic oligomers and insoluble amyloid plaques, which are central to the pathogenesis of Alzheimer's disease (NIH/NIA). Therapeutic targeting of the Aβ42 monomer, primarily through monoclonal antibodies like solanezumab, aims to sequester the soluble peptide to prevent its aggregation or to facilitate its clearance from the brain via the peripheral sink mechanism (PubMed 28103530). While monomer-specific therapies have struggled to demonstrate significant cognitive benefits in late-stage clinical trials compared to aggregate-preferring antibodies, Aβ42 remains a critical biomarker for disease progression, with low levels in cerebrospinal fluid indicating the accumulation of plaques in the brain (PubMed 30639447). Monitoring Aβ42 levels and its ratio to Aβ40 is essential for patient selection and evaluating the efficacy of anti-amyloid therapies in clinical practice (PubMed 33034469).

Other names

Amyloid-beta peptide 1-42Beta-amyloid 42Abeta42Aβ1-42Amyloid beta-protein 42

Monoclonal antibodies bind to soluble Aβ42 monomers to sequester them, preventing their aggregation into neurotoxic oligomers and plaques, and potentially facilitating clearance from the brain via the peripheral sink mechanism (PubMed 28103530).