Aggregated beta-amyloid fibril (Aβ fibril)

Aggregated beta-amyloid fibrils are insoluble protein structures generated from the self-assembly of beta-amyloid (Aβ) peptides via a nucleation-dependent pathway. These fibrils are stabilized by intermolecular hydrogen bonds in a parallel, in-register cross-β-sheet motif and are morphologically characterized by increased length and thickness as they mature[1][3][5][9]. Aβ fibrils, along with soluble oligomers and protofibrils, are central to the development of amyloid plaques in Alzheimer’s disease, driving neurotoxicity, inflammation, and synaptic loss through multiple pathways, including microglial activation and contact system-mediated vascular effects[1][2][4][6]. Therapeutic targeting of aggregated beta-amyloid fibrils (and their intermediates) forms the basis of several monoclonal antibody strategies, with agents such as lecanemab showing clinical benefits by reducing protofibril-induced toxic signaling and accelerating amyloid clearance[2][10]. Additional drug discovery efforts target co-factor interactions, aggregation mechanisms, and innate immune pathways involved in amyloid fibril assembly and removal[4][8]. This entity is most accurately classified not as a classical receptor, enzyme, or transporter, but as a pathogenic protein aggregate and a molecular target for disease-modifying therapies in Alzheimer’s disease.

Other names

beta-amyloid fibrilamyloid-beta fibrilAβ fibrilamyloid plaques (context-dependent)Alzheimer amyloid fibril

Direct antibody-mediated clearance of fibrils/protofibrils by microglial phagocytosis Inhibition of aggregation and seeding Disruption of peptide–cofactor interactions, reducing aggregation Enhanced uptake/degradation by innate immune cells