Activation of PKR can cause accumulation of amyloid β-peptide (Aβ) via de-repression of BACE1 (ß-site APP Cleaving Enzyme) expression in Alzheimer Disease patients. Normally, the 5′untranslated region (5′UTR) in the BACE1 promoter would fundamentally inhibit the expression of BACE1 gene. However, BACE1 expression can be activated by phosphorylation of eIF2a, which reverses the inhibitory effect exerted by BACE1 5′UTR. Phosphorylation of eIF2a is triggered by activation of PKR. Viral infection such as Herpes Simplex Virus (HSV) or oxidative stress can both increase BACE1 expression through activation of PKR-eIF2a pathway.