INSR and Alzheimer disease: The premise of this work stemmed from human and experimental data showing that AD is associated with impairments in brain insulin and IGF signaling [1,9,53-56], due in part to reduced trophic factor levels, receptor binding, receptor tyrosine kinase activation, and downstream signaling through insulin receptor substrate, PI3 Kinase and Akt [1,5,9,16,17,55].