Transgenic mouse models now exist that mimic a range of AD-related pathologies. Table 1 contains a summary of some of the more widely studied mouse models. As discussed later, these models have suggested new insights into the pathophysiology as well as novel therapeutic approaches. The models, however, raise a number of issues as well. First, it is clear that the success of transgenic mouse models has depended on the overexpression of APP transgenes containing FAD-associated mutations at levels that are not physiological. Indeed, many proteins, if overexpressed at sufficient levels, will become toxic at some point. It might be argued, therefore, that it is hardly surprising that overexpressing a naturally amyloidogenic protein would lead to amyloid deposits. However, interestingly, even though a number of APP wild transgenic lines have been created, only 1 transgenic mouse line overexpressing wild-type APP has been described that develops plaques.47 Thus, in general, overexpression of wild-type APP in the mouse does not induce plaque pathology, and the pathology that is seen seems to require the presence of an FAD mutation.
