Amyloid-beta peptide aggregate (Aβ aggregate) (Aβ aggregate)

Amyloid-beta peptide aggregates are insoluble clusters of misfolded proteins derived from the proteolytic cleavage of the amyloid precursor protein (APP) by beta- and gamma-secretases (UniProt: P05067). These aggregates exist in various forms, including soluble oligomers, protofibrils, and insoluble fibrils that deposit as extracellular senile plaques in the brain parenchyma (NIH: National Institute on Aging). In Alzheimer's disease, the accumulation of these aggregates is hypothesized to trigger a pathological cascade involving neuroinflammation, tau hyperphosphorylation, and synaptic dysfunction, ultimately leading to neuronal death (PubMed: PMC7246022). While the physiological role of monomeric Aβ remains debated, the aggregated forms are widely considered neurotoxic and central to the amyloid hypothesis of neurodegeneration (PubMed: 30612631). Therapeutic strategies primarily focus on using monoclonal antibodies to target and clear these aggregates or prevent their formation (StatPearls: Alzheimer Disease). Recent clinical successes with drugs like lecanemab and donanemab have validated Aβ aggregates as a primary therapeutic target for slowing cognitive decline in early-stage patients (PubMed: 36599520). These drugs work by binding to specific aggregate species and promoting their clearance via microglial phagocytosis (PubMed: 37459977). However, targeting these aggregates is associated with significant safety risks, most notably amyloid-related imaging abnormalities (ARIA), which include edema and microhemorrhages (PubMed: 37459977). Monitoring for ARIA via MRI is a standard requirement for patients receiving anti-amyloid therapies (FDA: Leqembi Prescribing Information). Despite challenges, Aβ aggregates remain the most heavily researched and clinically targeted feature of Alzheimer's pathology.

Other names

Amyloid-beta plaqueAβ oligomerAβ fibrilBeta-amyloid aggregateSenile plaqueAmyloid-beta protein aggregateAbeta aggregate

Monoclonal antibodies bind to specific epitopes on amyloid-beta oligomers, protofibrils, or insoluble fibrils, facilitating their clearance from the brain through microglial-mediated phagocytosis or direct dissolution of plaques (PubMed: 36599520).