 Viral infection such as Herpes Simplex Virus (HSV) or oxidative stress can both increase BACE1 expression through activation of PKR-eIF2a pathway.In addition, the increased activity of BACE1 could also lead to β-cleaved carboxy-terminal fragment of β-Amyloid precursor protein (APP-βCTF) induced dysfunction of endosomes in AD.Endosomes are highly active β-Amyloid precursor protein (APP) processing sites, and endosome abnormalities are associated with upregulated expression of early endosomal regulator, rab5.