Amyloid-beta oligomer and aggregate (Aβ oligomer/aggregate)

Amyloid-beta (Aβ) oligomers and aggregates are misfolded protein species derived from the proteolytic cleavage of the amyloid precursor protein (APP) by beta- and gamma-secretases. While insoluble Aβ fibrils constitute the core of senile plaques, soluble Aβ oligomers are widely recognized as the primary neurotoxic species responsible for synaptic loss and cognitive decline in Alzheimer's disease (Source: PubMed PMID: 18552855). A specific pathological manifestation of these oligomers is the formation of 'conducting Aβ pores' or ion-like channels that insert into neuronal membranes, causing uncontrolled calcium influx and subsequent cell death (Source: Nature Communications, DOI: 10.1038/ncomms1410). Therapeutic interventions, such as the FDA-approved monoclonal antibodies lecanemab and donanemab, target these aggregates to facilitate their clearance from the brain or neutralize their toxic effects (Source: New England Journal of Medicine, DOI: 10.1056/NEJMoa2212948). Despite their clinical efficacy in slowing disease progression, these therapies are often limited by safety concerns like Amyloid-Related Imaging Abnormalities (ARIA), which result from the disruption of the blood-brain barrier during the clearance of vascular amyloid (Source: Lancet Neurology, DOI: 10.1016/S1474-4422(23)00210-9).

Other names

Amyloid-beta poreAmyloid-beta ion channelAβOAmyloid-beta protofibrilSoluble Aβ oligomerPathological Aβ aggregate

Monoclonal antibody-mediated clearance of aggregates via microglial phagocytosis, neutralization of toxic soluble oligomers, and inhibition of Aβ pore-mediated membrane permeabilization.