INS and Alzheimer disease: The issue of insulin resistance and diabetes mellitus is important because epidemiological studies support that type 2 diabetes is a major contributor to AD risk (Cermakova et al., 2015; Ramos-Rodríguez et al., 2015; Sato and Morishita, 2015), and growing evidence supports the key concept that Alzheimer's disease is a metabolic disease, mediated by impairments in brain insulin responsiveness, glucose utilization, and energy metabolism, which ultimately lead to increased oxidative stress, inflammation, and worsening of insulin resistance (De la Monte, 2014).