Amyloid-beta aggregate (Aβ aggregate)

Amyloid-beta (Aβ) aggregates are misfolded protein assemblies derived from the proteolytic cleavage of the amyloid precursor protein (APP) by beta- and gamma-secretases. These aggregates exist in a continuum of forms, ranging from small, soluble oligomers and protofibrils to large, insoluble fibrils that deposit as amyloid plaques in the brain parenchyma. Soluble Aβ oligomers are widely considered the most neurotoxic species, as they disrupt synaptic plasticity, induce oxidative stress, and trigger downstream tau pathology and neuroinflammation. In Alzheimer's disease, the accumulation of these aggregates is a primary pathological hallmark and a central focus of the 'amyloid cascade hypothesis.' Therapeutic strategies targeting Aβ aggregates primarily involve monoclonal antibodies designed to recognize and clear these toxic species from the brain. Recent clinical successes with drugs like lecanemab and donanemab have validated Aβ aggregates as a viable therapeutic target for slowing cognitive decline in early-stage Alzheimer's patients.

Other names

Amyloid-beta oligomerAmyloid-beta fibrilAβ plaqueAmyloid-beta protein aggregateAbeta aggregateSoluble Aβ oligomer

Monoclonal antibodies bind to specific epitopes on Amyloid-beta aggregates (oligomers, protofibrils, or insoluble plaques) to facilitate their clearance via microglial phagocytosis or to neutralize their neurotoxic effects.