To define the relations and synergism between amyloid and Tau pathology in AD, and of the role of the GSK3 kinases, double transgenic mice were developed by combining homozygous Tau.P301L mice with either heterozygous human GSK3β.[S9A] mice or APP.V717I mice [77, 78, 114, 115], resulting, respectively, in GSK3βxTau.P301L (biGT) and APP.V717IxTau.P301L (biAT) bigenic mice. This evidence concerns the gene APP and Alzheimer disease.