Following the discovery of insulin and insulin receptors (IR) in the brain [7,8], and their abundance in brain regions involved in the regulation of cognitive function and metabolism [9], Hoyer and colleagues proposed dysfunctional brain insulin signaling might be involved in the development of the metabolic dyshomeostasis recognized as an important early molecular event preceding neuropathological changes in AD [10,11]. The gene discussed is INS; the disease is Alzheimer disease.