EIF2AK2 and Insulin resistance: Importantly, inflammatory cytokine/PICR-signaling in neurons and the concomitant activation of the IRS-1-inactivating serine kinases JNK, IKKβ, and PKR lead to cerebral insulin resistance in AD which, in turn, promotes Tau hyperphosphorylation by enhancing the activity of the Tau kinase GSK-3β (Holscher, 2019; Akhtar and Sah, 2020).