Collectively, these studies suggest that (1) Aβ aggregation is a protective mechanism to entrap herpesviruses (and perhaps other pathogens), (2) herpesviruses trigger the main hallmarks of AD in human brain tissue models, (3) herpesvirus-induced interferon signaling can trigger Aβ production, and (4) APOE4 increases the effect of herpesviral reactivation on AD risk. This evidence concerns the gene APOE and Alzheimer disease.