Recent commentary in Neurotherapeutics by Nath critically addresses the earlier report by Tzeng et al. that aggressive antiviral treatment (AVT) against herpes simplex virus (HSV) was associated with a later decrease in the incidence of Alzheimer's disease (AD). Nath raises issues that we respond to: we point out that (i) the treated group (probably with severe infection) is likely to harbor genetic risk alleles that predispose to both AD and HSV infection-the potential treatment bias cited by Nath would support (rather than challenge) the preventive effect of AVT; (ii) HSV is well known to establish persistent infection in the brain; and (iii) current AVT compounds used to combat herpes viruses are highly specific for this class of viruses. Instead of "alternative fact," the findings of Tzeng et al. argue in favor of clinical trials of AVT in AD.
Keywords: APOE; Acyclovir; Alzheimer's disease; Herpes simplex virus.