Expression of BRI-amyloid beta peptide fusion proteins: a novel method forspecific high-level expression of amyloid beta peptides

In order to develop transgenic animal models that selectively overexpress v arious A beta peptides, we have developed a novel expression system that se lectively expresses A beta 40 or A beta 42 in the secretory pathway. This s ystem utilizes fusion constructs in which the sequence encoding the 23-amin o-acid ABri peptide at the carboxyl terminus of the 266-amino-acid type 2 t ransmembrane protein BRI is replaced with a sequence encoding either A beta 40 or A beta 42. Constitutive processing of the resultant BRI-A beta fusio n proteins in transfected cells results in high-level expression and secret ion of the encoded A beta peptide. Significantly, expression of A beta 42 f rom the BRI-A beta 42 construct resulted in no increase in secreted A beta 40, suggesting that the majority of A beta 42 is not trimmed by carboxypept idase to A beta 40 in the secretory pathway. (C) 2001 Elsevier Science B.V. All rights reserved.