Moreover, an increasing number of studies have suggested that the brain itself becomes insulin-resistant and mediates or even triggers key pathophysiological events in AD (Rivera et al., 2005; Steen et al., 2005; Salkovic-Petrisic and Hoyer, 2007; Liu et al., 2011; Nuzzo et al., 2015; Rad et al., 2018; Akhtar and Sah, 2020). This evidence concerns the gene INS and Alzheimer disease.