The underlying mechanisms were proposed to involve accumulation of brain amyloid-β plaque pathology even in cognitively healthy subjects [4, 5], cognitive injury prior to the development of plaque pathology as in mice expressing the human APOE ε4 and human APP with familial AD mutations [6], or altered brain insulin signaling [7, 8] and glucose metabolism [9, 10] resulting in brain insulin resistance and cerebral glucose hypometabolism [11–13]. The gene discussed is INS; the disease is Alzheimer disease.