Amyloid beta peptide (Aβ) (Aβ)

The amyloid beta peptide (Aβ), primarily the 40-42 amino acid isoforms Aβ40 and Aβ42, is generated through sequential proteolytic cleavage of the transmembrane amyloid precursor protein (APP) by β-secretase (BACE1) and γ-secretase. In physiological contexts, Aβ participates in metal chelation (binding copper, zinc, iron) and modulates synaptic function, with low picomolar concentrations of monomers supporting neurotransmission and neuroprotection. Pathologically, elevated Aβ levels lead to self-assembly into soluble oligomers, protofibrils, and insoluble fibrils forming amyloid plaques characteristic of Alzheimer's disease (AD), driving neurotoxicity, synaptic dysfunction, inflammation, and neurodegeneration. Aβ42 exhibits higher fibrillogenic propensity due to its hydrophobic C-terminus, forming β-sheet-rich structures with intermolecular parallel β-sheets in residues 18-26 and 31-42. Therapeutic strategies target Aβ as a central AD driver via the amyloid cascade hypothesis, including anti-Aβ monoclonal antibodies (e.g., lecanemab, aducanumab) that clear plaques and oligomers, aggregation inhibitors (e.g., PBT2), and production reducers (e.g., BACE inhibitors, though many failed clinically). Approved agents like lecanemab reduce plaque burden and slow cognitive decline but carry risks like ARIA. Despite challenges, Aβ remains a key modifiable target for disease-modifying AD therapies.

Other names

beta-amyloidAbeta

Inhibition of Aβ aggregation and fibril formation, Promotion of Aβ clearance via phagocytosis, Reduction of Aβ production by targeting secretases or APP, Neutralization of Aβ oligomers and protofibrils, Peripheral sequestration of Aβ