systems were created by the replacement of the 23–amino acid BRI peptide region with human Aβ40 or Aβ42 sequences. Thus, in the fusion construct, cleavage, rather than releasing the native BRI peptide, releases either human Aβ40 or Aβ42. Although highly artificial constructs, the Bri-Aβ40 and Bri-Aβ42 transgenes offer an elegantly simple system for introducing human Aβ40 or Aβ42 into the mouse brain. Insoluble Aβ42 accumulated with aging in BRI-Aβ42 transgenic mice and was accompanied by amyloid deposition in the parenchyma in the form of both plaques and diffuse deposits as well as extensive vascular amyloid deposition. By contrast, BRI-Aβ40 mice developed no amyloid pathology at any age. These studies are thus consistent with Aβ42 being required for parenchymal and vascular deposits of Aβ40, and indeed, more recent studies have shown that BRI mice expressing high levels of Aβ40 are protected against amyloid deposition when bred with BRI-Aβ42 mice.71
