Amyloid-beta peptide (Abeta) (Abeta)

Amyloid-beta (Aβ) is a peptide of 36–43 amino acids that is the primary component of the amyloid plaques found in the brains of patients with Alzheimer's disease (UniProt P05067). It is produced through the sequential proteolytic cleavage of the Amyloid-beta precursor protein (APP) by beta-secretase (BACE1) and gamma-secretase (Selkoe & Hardy, 2016). In pathological states, Aβ monomers aggregate into soluble oligomers, protofibrils, and insoluble fibrils, which are thought to be the primary drivers of neurotoxicity (Hardy & Higgins, 1992). These aggregates disrupt synaptic transmission, induce oxidative stress, and trigger a neuroinflammatory response involving microglial activation (Jack et al., 2018). The Amyloid Hypothesis posits that the accumulation of Aβ is the fundamental cause of Alzheimer's disease, initiating a cascade that includes tau protein hyperphosphorylation and neuronal death (Selkoe & Hardy, 2016). Therapeutic interventions have focused on reducing Aβ levels through secretase inhibition or enhancing clearance via passive immunotherapy with monoclonal antibodies (FDA, 2023). Drugs such as Lecanemab and Aducanumab specifically target aggregated forms of Aβ to reduce plaque burden in the brain (FDA, 2023). Clinical monitoring of these therapies often involves assessing Amyloid-related imaging abnormalities (ARIA), which represent a significant safety concern (Sperling et al., 2011). Biomarkers such as the CSF Aβ42/Aβ40 ratio and Amyloid PET imaging are essential for patient selection and monitoring treatment efficacy (Jack et al., 2018).

Other names

Beta-amyloidA-betaAmyloid-betaAβAbeta peptide

Monoclonal antibodies bind to specific species of amyloid-beta (such as monomers, oligomers, protofibrils, or plaques) to neutralize their toxicity and promote clearance from the brain via microglial-mediated phagocytosis. Other mechanisms include the inhibition of beta-secretase (BACE1) or gamma-secretase to reduce the production of the peptide from its precursor protein.