The pathophysiological mechanisms thought to cause AD include impaired amyloid-beta and tau protein metabolism and neurodegeneration leading to regional and whole brain atrophy (according to the amyloid cascade hypothesis; Hardy and Higgins, 1992; Karran et al., 2011; Jack and Holtzman, 2013; Jack et al., 2013); however, it is known that clinical progression of the disease does not always align with levels of neuropathology load. The gene discussed is MAPT; the disease is Alzheimer disease.