Amyloid-beta protein (Aβ)

Amyloid-beta protein fibrils are insoluble protein aggregates primarily composed of amyloid-beta (Aβ) peptides, which are derived from the proteolytic cleavage of the amyloid precursor protein (APP) by beta- and gamma-secretases (Hardy & Higgins, 1992, Science). These fibrils accumulate extracellularly in the brain parenchyma to form senile plaques, a defining pathological hallmark of Alzheimer's disease (Selkoe & Hardy, 2016, EMBO Molecular Medicine). While monomeric Aβ may play roles in synaptic modulation and antimicrobial defense, the aggregated forms—particularly soluble oligomers and insoluble fibrils—exert neurotoxic effects (Walsh & Selkoe, 2007, Journal of Neurochemistry). These toxic effects include the disruption of calcium homeostasis, induction of oxidative stress, and the triggering of chronic neuroinflammatory responses (Soscia et al., 2010, PLoS ONE). Therapeutic interventions have largely focused on the amyloid hypothesis, utilizing monoclonal antibodies like lecanemab and donanemab to clear these deposits from the brain (FDA, 2023, Leqembi Prescribing Information). These drugs work by binding to specific Aβ species and facilitating their removal via microglial-mediated phagocytosis (Sevigny et al., 2016, Nature). Clinical use of these agents requires careful monitoring for amyloid-related imaging abnormalities (ARIA), which represent significant safety concerns associated with the removal of vascular and parenchymal amyloid (Sperling et al., 2011, Alzheimer's & Dementia). Despite recent successes in plaque reduction, the degree to which clearing amyloid-beta fibrils translates to meaningful cognitive improvement remains a subject of intense clinical investigation (Mintun et al., 2021, New England Journal of Medicine).

Other names

Beta-amyloidA-betaBeta-amyloid peptideAβ42Aβ40Senile plaquesAmyloid-beta fibrilsAmyloid-beta plaques

Monoclonal antibodies bind to specific epitopes on amyloid-beta monomers, oligomers, or fibrils to promote clearance via microglial phagocytosis or to prevent further aggregation into neurotoxic plaques (Sevigny et al., 2016, Nature).