EIF2AK2 and Alzheimer disease: Elevated TNF-α seems to be a consequence of the brain accumulation and the impact of Aβ oligomers, which were demonstrated to induce brain IRS1 inhibition through a mechanism involving either reduced IR exposure at the plasma membrane (Zhao et al., 2008; De Felice et al., 2009; Forny-Germano et al., 2014) or increased ER stress via PKR (Lourenco et al., 2013) in AD (Figure 2).