Amyloid-beta 1-40 (Aβ40)

Amyloid-beta 1-40 (Aβ40) is a 40-amino acid peptide derived from the proteolytic processing of the amyloid precursor protein (APP) by beta- and gamma-secretases [UniProt P05067, NIH]. It is the most abundant isoform of amyloid-beta in the human brain and cerebrospinal fluid, typically existing as a soluble, intrinsically disordered monomer under physiological conditions [Wikipedia, NIH]. Under pathological conditions, Aβ40 can transition into a misfolded, aggregation-prone state, which serves as a critical early intermediate in the formation of toxic oligomers and insoluble amyloid fibrils [NIH, PubMed]. While Aβ42 is the primary component of parenchymal plaques in Alzheimer's disease, Aβ40 is the predominant species found in vascular amyloid deposits associated with cerebral amyloid angiopathy (CAA) [NIH, PubMed]. These vascular deposits contribute to neurovascular dysfunction, blood-brain barrier breakdown, and cerebral microhemorrhages [NIH]. Therapeutic strategies targeting Aβ40 include monoclonal antibodies like Ponezumab that promote clearance, small molecules like Tramiprosate that inhibit aggregation, and secretase inhibitors like Verubecestat aimed at reducing peptide production [NIH, PubMed].

Other names

Abeta 1-40Amyloid-beta protein 40Beta-amyloid 1-40Aβ40 monomerMisfolded Aβ40

Inhibition of amyloid aggregation, reduction of amyloid-beta production via secretase inhibition, promotion of amyloid clearance through antibody-mediated mechanisms, and stabilization of monomeric amyloid-beta to prevent toxic assembly.