These authors suggested that the key mechanism in the development of disease in the human AD, as well as in the rodent model disease is the development of brain insulin resistance which leads to neurofibrillary degeneration via two cooperating pathways, namely decreased PI3K-AKT signaling activity and glycogen synthase kinase 3 beta (GSK3β) overactivation and decreased GLUT1/3 expression and decreased intraneuronal glucose metabolism. This evidence concerns the gene INS and Alzheimer disease.