Amyloid-beta peptide assemblies (Aβ) (Aβ)

Amyloid-beta (Aβ) assemblies are protein aggregates formed by the proteolytic cleavage of the amyloid precursor protein (APP) by beta- and gamma-secretases (Hardy & Higgins, 1992). These assemblies exist in a dynamic equilibrium of species, including soluble monomers, neurotoxic oligomers, protofibrils, and insoluble fibrillar plaques that deposit in the brain parenchyma (Selkoe & Hardy, 2016). In Alzheimer's disease, the accumulation and aggregation of Aβ are central to the amyloid cascade hypothesis, which posits that Aβ deposition triggers a pathological sequence including tau hyperphosphorylation, neuroinflammation, and synaptic loss (Hardy & Higgins, 1992; Selkoe & Hardy, 2016). Therapeutic strategies primarily target these assemblies using monoclonal antibodies, such as lecanemab and donanemab, to enhance their clearance from the brain or prevent further aggregation (van Dyck et al., 2023; Mintun et al., 2021; Sevigny et al., 2016). Clinical evidence suggests that reducing the amyloid burden can slow cognitive decline in patients with early-stage Alzheimer's disease (van Dyck et al., 2023). However, targeting Aβ assemblies is associated with significant safety concerns, most notably Amyloid-Related Imaging Abnormalities (ARIA), which involve brain edema or microhemorrhages (Sperling et al., 2011). Additionally, Aβ assemblies are a hallmark of cerebral amyloid angiopathy, where they deposit within the walls of cerebral blood vessels (Jack et al., 2018).

Other names

Amyloid-betaA-betaAβAmyloid-beta proteinAmyloid-beta oligomersAmyloid-beta protofibrilsAmyloid-beta fibrilsAmyloid-beta plaquesAβ42Aβ40

Passive immunization with monoclonal antibodies to facilitate clearance of Aβ aggregates via microglial phagocytosis, inhibition of Aβ aggregation, and neutralization of soluble toxic oligomers (van Dyck et al., 2023; Sevigny et al., 2016).