Amyloid-β peptide fibril (Aβ fibril)

Amyloid-β peptide fibrils are insoluble, highly ordered protein aggregates formed by the polymerization of amyloid-β (Aβ) peptides, typically 38–43 amino acids long, most commonly Aβ40 and Aβ42[5][1][8]. These fibrils are fundamental components of amyloid plaques, which are a pathological hallmark of Alzheimer’s disease[1][3][4]. Structurally, Aβ fibrils exhibit a cross-β sheet configuration, where β-strands from individual peptides align perpendicularly to the fibril axis, often forming protofilaments that laterally associate into mature fibrils[2][7][8]. The aggregation of these peptides into fibrils is neurotoxic and contributes to neuronal dysfunction and cell death in neurodegenerative disease[1][5][4]. Aβ fibrils are a primary therapeutic target in Alzheimer’s disease, with approved drugs (such as aducanumab, lecanemab, and donanemab) and diagnostic agents directly targeting these aggregates[3][9]. The complexity and diversity (polymorphism) of Aβ fibril structure may influence disease progression, therapeutic response, and biomarker utility[8]. Development of therapies targeting Aβ fibrils faces challenges like immune-mediated brain inflammation, variable efficacy, and patient selection based on imaging and biomarker criteria[3][9].

Other names

Amyloid beta fibrilβ-amyloid fibrilAβ fibrilAmyloid-β fibrilAmyloid beta peptide fibrilAmyloid fibril (when specifically referring to β-amyloid)

Monoclonal antibodies bind to and facilitate clearance of Aβ fibrils and/or plaques - Inhibition of Aβ aggregation or promotion of disassembly - Modulation of immune-mediated removal