Given the availability of methods for introducing genetic modifications, modeling in transgenic mice has been vigorously pursued on the basis of the amyloid hypothesis.9–11 Initially, before the discovery of FAD mutations, attempts were made to overexpress wild-type APP in transgenic mice by pronuclear injection. Although a variety of promoters were tried, none of these efforts produced anything that resembled an amyloid plaque or any other recognizable AD-type pathology.
