PS1 FAD mutant transgenic lines have been generated with many of the same promoters used to create APP mice, including PDGF24 and PrP.25,26 A few PS2 FAD mutant lines also exist. In addition, several gene-targeted lines exist in which PS1 FAD mutations have been targeted to the endogenous mouse PS1.27–29 Presenilin FAD mutant mice consistently show elevations of Aβ42 with little if any effect on Aβ40. However, singly transgenic PS1 or PS2 mice do not develop plaques, although when crossed with plaque-forming APP lines, the presenilin FAD mutations cause earlier and more extensive plaque formation.30 Why singly transgenic PS1 and PS2 mice fail to develop plaque pathology is not entirely clear, but may be related to the generally lower levels of Aβ42 found in single presenilin transgenics versus APP-overexpressing lines as well as the lack of elevation of Aβ40 in presenilin transgenics. It may also be related to the differing aggregation properties of mouse Aβ versus human Aβ.31
