APP and Alzheimer disease: HSV-1 has been implicated in AD pathogenesis by several lines of evidence, including the presence of HSV-1 viral DNA in human brain tissue [50,51], increased HSV-1 seropositivity in AD cases [52–55], the correlation of high avidity HSV-1 antibodies with protection from cognitive decline [55], the binding of HSV-1 gB to APOE-containing lipoproteins [56], HSV-1-induced amyloidogenic processing of amyloid precursor protein (APP) [57–59], and preferential targeting of AD-affected regions in HSV-1 acute encephalitis [60].