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

Abstract 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.