Expression of BRI-amyloid β peptide fusion proteins: A novel method for specific high-level expression of amyloid β peptides

In order to develop transgenic animal models that selectively overexpress various Aβ peptides, we have developed a novel expression system that selectively expresses Aβ40 or Aβ42 in the secretory pathway. This system utilizes fusion constructs in which the sequence encoding the 23-amino-acid ABri peptide at the carboxyl terminus of the 266-amino-acid type 2 transmembrane protein BRI is replaced with a sequence encoding either Aβ40 or Aβ42. Constitutive processing of the resultant BRI-Aβ fusion proteins in transfected cells results in high-level expression and secretion of the encoded Aβ peptide. Significantly, expression of Aβ42 from the BRI-Aβ42 construct resulted in no increase in secreted Aβ40, suggesting that the majority of Aβ42 is not trimmed by carboxypeptidase to Aβ40 in the secretory pathway.