Transgenic animals have been widely used to study factors that affect Aβ deposition. For example, the role that apolipoprotein ε4 and its isoforms play in the development of plaque pathology has been extensively studied with apolipoprotein ε4 transgenic and knockout mice crossed to APP transgenic mice.83–85 Studies examining how dietary cholesterol affects plaque pathology in transgenic mice86 have formed part of the basis for proposals to use statin therapy for AD. Indeed, APP transgenic mice have been used to evaluate a variety of factors that influence Aβ production and plaque pathology; these factors range from inflammatory modulators, metal chelators, and natural products that bind Aβ to lifestyle factors including exercise, environmental enrichment, caloric restriction, and wine consumption.10,87–90
