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

Amyloid-beta (Aβ) fibrils are insoluble, highly ordered protein aggregates characterized by a cross-beta sheet structure, primarily composed of Aβ40 and Aβ42 peptides derived from the proteolytic cleavage of the amyloid precursor protein (APP) [1]. These fibrils are the principal component of extracellular senile plaques, which are a defining pathological hallmark of Alzheimer's disease (AD) [2]. The aggregation process involves the transition of soluble Aβ monomers into toxic oligomers and eventually into stable, insoluble fibrils that deposit in the brain parenchyma and vasculature [3]. In Alzheimer's disease, the accumulation of these fibers is linked to neuroinflammation, synaptic dysfunction, and the induction of tau pathology, ultimately leading to neurodegeneration [4]. Therapeutic strategies targeting Aβ fibrils include monoclonal antibodies such as aducanumab, lecanemab, and donanemab, which are designed to recognize aggregated Aβ species and promote their clearance via microglial phagocytosis [5]. While reducing the fibril burden is a primary goal of modern disease-modifying therapies, these treatments are frequently associated with amyloid-related imaging abnormalities (ARIA), which require careful clinical monitoring [6].

Other names

A-beta fiberAmyloid-beta aggregateAβ42 fibrilAβ40 fibrilSenile plaque componentAmyloid-beta plaque

Monoclonal antibodies bind to aggregated forms of amyloid-beta, including fibrils and plaques, to facilitate their clearance from the brain via microglial-mediated phagocytosis [5, 6].