Previous findings in transgenic mice overexpressing the familial AD mutant form of presenilin-1 (PS1) [34] or in conditional knockout PS1 mice generated on a PS2 null mutant background, show abnormal tau hyperphosphorylation, robust brain atrophy, impaired learning and memory and AD-like neurodegeneration in the absence of β-amyloid deposition [35]. This evidence concerns the gene PSEN1 and Alzheimer disease.