Amyloid beta protofibril and fibril (Aβ protofibril and fibril (Aβ PF/F))

Amyloid beta protofibrils and fibrils are aggregated forms of the amyloid-beta peptide, a cleavage product of the amyloid precursor protein in neural tissue[1][2][3][4][5]. Protofibrils are soluble, rod-like pre-fibrillar aggregates, whereas fibrils are insoluble, highly ordered structures with a cross-β-sheet motif, stabilized by hydrogen bonds and assembled perpendicularly to the long axis of the fibril[1][2][3][5]. These aggregated species exhibit significant structural polymorphism depending on conditions and may differ in neurotoxicity and stability[5]. Fibrillar amyloid beta accumulation is a pathological hallmark of Alzheimer’s disease and is associated with synaptic dysfunction, neuroinflammation, and neuronal loss[3][4][5]. Drug interventions, most notably monoclonal antibodies, target these aggregated structures either to neutralize their toxic effects, promote their clearance, or prevent further aggregation. Structural studies using solid-state NMR, X-ray crystallography, and cryo-EM have elucidated various conformations of Aβ40 and Aβ42, showing correlations between aggregate structure and disease progression[2][3][5]. Fibrillar amyloid beta commonly deposits as amyloid plaques in the brain, which can be visualized by amyloid imaging and used as diagnostic biomarkers[3][5]. Safety concerns for therapies primarily include amyloid-related imaging abnormalities and inflammation associated with rapid plaque removal[3].

Other names

Amyloid-beta protofibrilAmyloid-beta fibrilAβ protofibrilAβ fibrilAmyloid-beta (Aβ) aggregatesSoluble Aβ aggregatesFibrillar amyloid-betaAmyloid plaque (when deposited)

Antibody-mediated binding and clearance; Inhibition of aggregation/seed formation; Promotion of phagocytosis (by microglia); Direct disruption of fibril formation; Stabilization of non-toxic forms[4]