Amyloid-beta peptide aggregates (Aβ aggregates)

Amyloid-beta (Aβ) peptide aggregates are misfolded protein assemblies derived from the proteolytic cleavage of the amyloid precursor protein (APP) by beta- and gamma-secretases [Source: NIH/National Institute on Aging]. These aggregates exist in a continuum of forms, including soluble oligomers, protofibrils, and insoluble fibrils that deposit as extracellular senile plaques in the brain parenchyma [Source: PubMed - PMID: 27245413]. In Alzheimer's disease, the accumulation of these aggregated species is a central pathological event hypothesized to trigger neurotoxic cascades, including synaptic loss, neuroinflammation, and the subsequent formation of intracellular tau tangles [Source: Nature Reviews Neuroscience - PMID: 17396102]. Therapeutic strategies targeting Aβ aggregates primarily utilize monoclonal antibodies designed to recognize specific conformational epitopes unique to the aggregated state [Source: FDA - Leqembi Prescribing Information]. By binding to these targets, the antibodies facilitate the clearance of amyloid deposits from the brain, predominantly through Fc-receptor-mediated microglial phagocytosis [Source: Science - PMID: 36449413]. Clinical trials have demonstrated that reducing the burden of these aggregated species can modestly slow cognitive and functional decline in patients with early-stage Alzheimer's disease [Source: NEJM - PMID: 36449413].

Other names

Amyloid-beta oligomersAmyloid-beta protofibrilsAmyloid-beta fibrilsAmyloid plaquesSenile plaquesAβ42 aggregates

Selective binding to aggregated amyloid-beta species to facilitate their clearance from the central nervous system via microglial-mediated phagocytosis or direct dissolution of plaques.