Amyloid-beta oligomer (AβO) and pathogenic protein aggregate (AβO)

Amyloid-beta (Aβ) oligomers and other pathogenic protein aggregates are non-native, misfolded protein assemblies that play a central role in the pathogenesis of various neurodegenerative disorders (PubMed: 28959913). These aggregates, which include soluble oligomers, protofibrils, and insoluble fibrils, are formed through the polymerization of proteins such as Aβ, Tau, alpha-synuclein, and TDP-43. Unlike their monomeric counterparts, these aggregated species exhibit potent neurotoxicity by inducing synaptic dysfunction, membrane poration, and chronic neuroinflammation (NIH: NBK499922). In Alzheimer's disease, soluble Aβ oligomers are increasingly recognized as the most bioactive and toxic forms, correlating more closely with cognitive decline than insoluble plaques (PubMed: 17588960). Therapeutic interventions primarily focus on monoclonal antibodies that selectively bind these aggregates to promote their clearance via microglial phagocytosis or small molecules that inhibit the aggregation process (PubMed: 36630467). While drugs like lecanemab and donanemab have demonstrated clinical efficacy in slowing disease progression, safety concerns such as Amyloid-Related Imaging Abnormalities (ARIA) and the challenge of targeting multiple co-existing protein pathologies remain critical considerations in drug development (PubMed: 37455477).

Other names

Toxic protein oligomersAmyloidogenic proteinsMisfolded protein assembliesProteopathic aggregatesAmyloid fibrilsPathogenic protein inclusions

Immunotherapy-mediated clearance of aggregates via microglial phagocytosis; small molecule inhibition of protein misfolding and nucleation-dependent polymerization.