Amyloid-beta fibril (Aβ fibril)

Amyloid-beta fibril Overview

Amyloid-beta fibril refers to an aggregated, insoluble, and highly ordered structure of the amyloid-beta (Aβ) peptide, most often comprising the Aβ(1-40) or Aβ(1-42) isoforms. These fibrils are characterized by a cross-β-sheet quaternary structure, in which β-strands run perpendicular and hydrogen bonds run parallel to the fibril axis, forming highly stable and protease-resistant fibers[1][3][5]. Amyloid-beta fibrils are the main constituents of neuritic plaques found in the brains of patients with Alzheimer’s disease, and their formation is a hallmark pathological event linked with neurodegeneration. The process of fibril formation involves the aggregation of soluble Aβ monomers through oligomeric intermediates into mature fibrils, which deposit extracellularly in brain tissue. These structures are implicated in neurotoxicity, synaptic dysfunction, and the progression of Alzheimer’s disease, making them a key therapeutic target for disease-modifying treatments. Numerous monoclonal antibodies and amyloid-lowering agents targeting these fibrils have entered clinical development, demonstrating the recognition of amyloid-beta fibrils as a central and actionable target in Alzheimer’s disease therapy[2][4][6].

Mechanism of Action

Antibody-mediated clearance (monoclonal antibodies bind fibrils and promote immune-mediated clearance), Inhibition of fibril formation (by inhibiting β- or γ-secretase), Prevention of protein aggregation, Promotion of proteolytic degradation

Biological Functions

Safety Considerations

Interacting Drugs

Associated Biomarkers