Amyloid-beta A4 protein oligomer (AβO) (AβO)

Amyloid-beta (Aβ) oligomers are soluble, intermediate aggregates of the Aβ peptide, which is derived from the proteolytic cleavage of the Amyloid Precursor Protein (APP) (Selkoe & Hardy, 2016). While amyloid plaques were historically the focus of Alzheimer's research, current evidence suggests that these smaller, soluble oligomeric forms are the primary drivers of neurotoxicity and synaptic loss (Haass & Selkoe, 2007). They disrupt neuronal signaling by binding to synaptic receptors and inhibiting long-term potentiation, eventually leading to cell death. In Alzheimer's disease, the accumulation of these toxic species correlates more closely with cognitive decline than the density of insoluble plaques. Therapeutic interventions like lecanemab and ACU193 are designed to specifically target and neutralize these oligomers or their larger protofibrillar precursors (van Dyck et al., 2023). By clearing these toxic aggregates, these drugs aim to preserve synaptic function and slow the progression of neurodegeneration.

Other names

Amyloid-beta oligomerSoluble Aβ oligomerAβ protofibrilToxic Aβ speciesAmyloid-beta 42 oligomerAβO

Monoclonal antibodies selectively bind to misfolded oligomeric or protofibrillar forms of Amyloid-beta, neutralizing their neurotoxic effects and facilitating their clearance from the brain via microglial phagocytosis (van Dyck et al., 2023; Sevigny et al., 2016).