Several neurodegenerative features have been established as a consequence of systemic IR in AD, including metabolic and mitochondrial dysfunction (increased oxidative stress) (Wilkins et al., 2014), impaired systemic insulin signaling and miRNA deregulation (formation of NFTs) (Liu et al., 2014), neuroinflammation (activation of microglia and pro-inflammatory cytokines) (Gaspar et al., 2016; Chowdhury et al., 2018), impaired leptin signaling (loss of synaptic plasticity) (Arnold et al., 2018) and accelerated Aβ plaque formation (Petrov et al., 2015; Sallam et al., 2015). This evidence concerns the gene INS and Alzheimer disease.