Amyloid-beta aggregated fibril or oligomer (Aβ (for Amyloid-beta); Aβ oligomer; Aβ fibril)

Amyloid-beta aggregates include both fibrils (ordered, insoluble deposits) and oligomers (small, soluble aggregates), each formed by misfolding and self-association of amyloid-beta peptides, primarily Aβ1–42 or Aβ1–40[3][5][1]. Oligomers are now considered the most neurotoxic species and a key pathogenic driver of Alzheimer’s disease, disrupting neuronal membranes, impairing synaptic function, triggering inflammation, and ultimately causing neurodegeneration[2][8]. Aggregation follows a nucleation-dependent process, beginning with oligomers, then forming protofibrils and mature fibrils[5]. Both forms are characterized structurally by a high content of β-sheet secondary structure and display polymorphism. They interact with various neuronal receptors, and targeting these aggregates (especially oligomers) is a major focus of Alzheimer’s research and drug development, with several monoclonal antibodies and other strategies aiming to reduce aggregate burden or toxicity approved or in clinical trials[6][8][2]. Despite therapeutic promise, interventions targeting these aggregates must address challenges such as immune side effects, incomplete efficacy, and complex polymorphic structures.

Other names

Amyloid-beta aggregateAggregated amyloid-betaAmyloid-beta oligomerAmyloid-beta fibrilAβ aggregateAβ oligomerAβ fibril

Antibody-mediated clearance of amyloid aggregates (Aducanumab, Lecanemab, Donanemab)[6]; Direct binding to and neutralization of oligomers or fibrils; Disruption of aggregate assembly (by small molecules, peptides, or nanoparticles)[2][8]; Prevention of new aggregate (oligomer/fibril) formation; Inhibition of receptor-mediated toxicity (targeting putative oligomer binding to receptors like Prion protein, EphA4, mGluR5, NMDA receptor, etc.)[4]; Enhancement of aggregate clearance via microglia (immunotherapy).