After the discovery of FAD mutations in APP, a number of groups turned their attention to making AD models based on the overexpression of transgenes containing FAD mutations. Games et al. 12 reported the first successful application of this approach using a platelet derived growth factor-β (PDGF) promoter to drive a human APP transgene that contained an FAD associated mutation (V717F). The PDGF promoter was chosen because, despite its name, it was known to be highly expressed in the central nervous system and to drive strong expression of exogenous transgenes in neurons. In the line that was generated (termed PDAPP because of the PDGF promoter plus APP), 40 copies of the transgene integrated, and this resulted in an approximately 18-fold elevation of APP RNA and an approximately 10-fold elevation of human APP protein in comparison with endogenous mouse APP levels. Proportionate increases in human Aβ were found.
