Importantly, the familial AD mouse models differ not only from the sporadic disease, but they also differ from the familial AD patients, as evident in brain pathology components, particularly the lack of the tangle pathology, a major limitation since tau burden correlate best with dementia, in terms of severity and distribution of the tangles in human brains, better than β-amyloid- plaque burden [47, 48]. This evidence concerns the gene MAPT and Alzheimer disease.