Amyloid-beta 40 (Aβ40) (Aβ40)

Amyloid beta 40 (Aβ40) is a 40-amino acid peptide generated from the amyloid precursor protein (APP) through sequential cleavage by beta- and gamma-secretases (UniProt P05067). It is the most prevalent isoform of the amyloid-beta peptides found in the cerebrospinal fluid and is a major constituent of vascular amyloid deposits in cerebral amyloid angiopathy (CAA) (PubMed: 23813751). The C-terminal epitope of Aβ40 is unique compared to the Aβ42 isoform, ending at Valine-40, which allows for highly specific therapeutic targeting using monoclonal antibodies like ponezumab (PubChem CID: 156025801). These therapies aim to reduce the amyloid burden in the brain by sequestering soluble Aβ40 in the periphery or facilitating its efflux from the brain (PubMed: 20854144). While Aβ40 is often considered less neurotoxic than Aβ42, its accumulation in the cerebrovasculature contributes significantly to stroke risk and cognitive decline in elderly populations. Clinical development of Aβ40-specific agents has focused on Alzheimer's disease and CAA, though safety concerns such as amyloid-related imaging abnormalities (ARIA) remain a significant hurdle (PubMed: 28234211). Targeting the C-terminus specifically avoids interference with the amyloid precursor protein or other Aβ variants, potentially improving the safety profile compared to pan-Aβ antibodies.

Other names

Beta-amyloid 1-40Abeta40Aβ1-40Amyloid-beta peptide 40Amyloid beta 40 C-terminal epitope

Selective binding to the C-terminal epitope of soluble Amyloid beta 40 (Aβ40) to facilitate its clearance from the brain via the peripheral sink mechanism or direct neutralization of soluble species (PubMed: 20854144).