Amyloid-beta peptide (Aβ) aggregates (Aβ)

Amyloid-beta (Aβ) aggregates are extracellular accumulations of misfolded peptides derived from the proteolytic cleavage of the amyloid precursor protein (APP) by beta- and gamma-secretases (Selkoe & Hardy, 2016, Nature Medicine). These aggregates exist in a continuum of states, including soluble monomers, toxic oligomers, protofibrils, and insoluble fibrils that form the core of senile plaques (Jack et al., 2018, Alzheimer's & Dementia). While Aβ monomers may have physiological roles in synaptic plasticity and antimicrobial defense, their aggregation is a central event in the amyloid cascade hypothesis of Alzheimer's disease, leading to neuroinflammation, synaptic loss, and eventual neuronal death (Hardy & Higgins, 1992, Science). Therapeutic interventions targeting Aβ aggregates, such as the FDA-approved monoclonal antibodies lecanemab and donanemab, aim to reduce plaque burden and slow cognitive decline by facilitating microglial clearance of the protein (van Dyck et al., 2023, NEJM). However, these therapies are associated with amyloid-related imaging abnormalities (ARIA), which represent a significant safety concern involving brain edema or hemorrhage (Sperling et al., 2011, Alzheimer's & Dementia).

Other names

Amyloid-beta plaquesAβ plaquesSenile plaquesNeuritic plaquesAmyloid-beta fibrilsAmyloid-beta oligomersAbeta aggregates

Monoclonal antibodies bind to specific conformational epitopes of amyloid-beta (such as protofibrils or insoluble plaques) to facilitate their clearance from the brain via microglial-mediated phagocytosis or to neutralize soluble toxic species.