Amyloid beta peptide 40 (Aβ40)

Amyloid beta peptide 40 (Aβ40) is a 40-amino acid peptide derived from the amyloid precursor protein (APP) through sequential proteolytic cleavage by beta-secretase and gamma-secretase (UniProt P05067). It is the most prevalent isoform of the amyloid-beta peptide in the human brain and cerebrospinal fluid, though it is less prone to initial aggregation than the Aβ42 isoform (PubMed: 21561155). Aβ40 plays a central role in the development of cerebral amyloid angiopathy (CAA), where it preferentially deposits within the walls of cerebral blood vessels, leading to vascular dysfunction and hemorrhage (PubMed: 22123313). The C-terminal epitope of Aβ40, ending at Valine-40, provides a unique structural feature that allows for the development of highly selective monoclonal antibodies (AlzForum: Ponezumab). These therapeutic agents, such as ponezumab, are designed to bind specifically to Aβ40 without cross-reacting with Aβ42 or the parent APP, thereby facilitating the clearance of soluble amyloid from the central nervous system (PubMed: 22585301). By reducing the concentration of Aβ40, these drugs aim to mitigate both vascular amyloid burden and the progression of Alzheimer's disease-related pathology.

Other names

Beta-amyloid 1-40Abeta40A-beta-40Amyloid-beta 40APP-derived amyloid-beta 40

Selective binding to the C-terminal epitope of Aβ40 to facilitate its clearance from the brain and vasculature via the peripheral sink mechanism or Fc-mediated phagocytosis, thereby preventing the formation of vascular amyloid deposits (PubMed: 22585301).