Amyloid-beta protein fibril (Aβ fibril) (Aβ fibril)

Amyloid-beta (Aβ) protein fibrils are insoluble, misfolded aggregates of the Aβ peptide, primarily the Aβ42 isoform, which constitute the core of senile plaques in Alzheimer's disease [1]. These fibrils form through a complex aggregation pathway where soluble monomers transition into toxic oligomers and protofibrils before stabilizing into cross-beta sheet fibrillar structures [1]. In the central nervous system, the accumulation of fibrillar Aβ is linked to neurotoxicity, synaptic dysfunction, and the induction of neuroinflammatory responses [1, 4]. The presence of these aggregates is a defining pathological hallmark of Alzheimer's disease and is thought to precede and trigger the formation of neurofibrillary tangles composed of tau protein [1]. Therapeutic targeting of these aggregates has focused on monoclonal antibodies, such as lecanemab and donanemab, which bind to fibrillar or protofibrillar forms to promote their clearance via microglial-mediated phagocytosis [2, 3, 6]. Clinical trials have demonstrated that reducing the burden of fibrillar amyloid in the brain can significantly slow the rate of cognitive and functional decline in patients with early-stage Alzheimer's disease [5, 6]. Beyond Alzheimer's, fibrillar Aβ also deposits in the walls of cerebral blood vessels, leading to cerebral amyloid angiopathy and an increased risk of hemorrhage [1].

Other names

Fibrillar amyloid-betaAmyloid-beta aggregatesAβ42 fibrilsInsoluble amyloid-betaSenile plaquesAmyloid-beta protein (Aβ) fibrils

Monoclonal antibodies target specific epitopes on aggregated amyloid-beta, including protofibrils and mature fibrils, to facilitate their removal from the brain through Fc-receptor mediated phagocytosis by microglia and potentially through the 'sink effect' or direct plaque dissolution [2, 3, 4].