Amyloid-beta oligomer formation pathway (Aβ oligomerization)

The Amyloid-beta (Aβ) oligomer formation pathway is a central pathological process in Alzheimer's disease, involving the misfolding and self-association of Aβ monomers into soluble, highly neurotoxic oligomers [3, 6]. These oligomers are considered the primary drivers of synaptic dysfunction and neuronal death, often preceding the formation of insoluble amyloid plaques [5, 9]. The pathway encompasses primary nucleation, where monomers aggregate, and secondary nucleation, where existing fibrils catalyze the formation of new oligomers [12, 14]. Therapeutic strategies targeting this pathway aim to inhibit the aggregation process, neutralize toxic oligomeric species, or promote their clearance from the brain using monoclonal antibodies or small-molecule inhibitors [1, 8]. Recent clinical successes with agents like lecanemab and donanemab have validated the reduction of aggregated Aβ as a viable disease-modifying approach [1, 10]. However, the heterogeneity of oligomer species and the risk of Amyloid-Related Imaging Abnormalities (ARIA) remain significant challenges in drug development [1, 14].

Other names

Amyloid-beta aggregation pathwayAmyloid-beta cascadeAβ oligomerizationSoluble amyloid-beta oligomer formationAβ42 oligomerization pathway

Inhibition of amyloid-beta monomer aggregation, clearance of soluble oligomers and protofibrils via antibody-mediated phagocytosis, and neutralization of neurotoxic amyloid-beta species to prevent synaptic damage.