Amyloid-beta (Aβ) (Aβ)

Amyloid-beta (Aβ) is a peptide of 36–43 amino acids derived from the proteolytic cleavage of the amyloid precursor protein (APP) by beta- and gamma-secretases (UniProt: P05067). It is the primary constituent of the extracellular senile plaques that characterize Alzheimer's disease pathology (StatPearls, 2024). While monomeric Aβ may play physiological roles in synaptic plasticity and antimicrobial defense, its transition into soluble oligomers and insoluble fibrils is highly neurotoxic (PubMed: 28913144). These aggregates interfere with synaptic function, induce oxidative stress, and trigger a cascade of neuroinflammation and tau protein hyperphosphorylation. In the context of drug development, Aβ is a major therapeutic target, with several monoclonal antibodies designed to bind and clear these deposits from the brain. Drugs such as lecanemab and donanemab specifically target protofibrils and plaques to reduce the amyloid burden and slow clinical progression in early-stage patients (FDA, 2023). However, targeting Aβ is associated with significant safety risks, most notably amyloid-related imaging abnormalities (ARIA), which require careful monitoring via MRI.

Other names

Beta-amyloidAbetaA-betaAmyloid-beta peptideAβ42Aβ40Amyloid-beta plaquesSoluble Aβ oligomers

Monoclonal antibodies bind to specific epitopes on amyloid-beta monomers, oligomers, or insoluble plaques to facilitate their clearance via microglial-mediated phagocytosis or to neutralize toxic species and prevent further aggregation (PubMed: 33135015; FDA, 2023).