Interaction between APOE4 and herpes simplex virus type 1 in Alzheimer's disease.

INTRODUCTION: Numerous results suggest the implication of infectious agents in the onset of Alzheimer's disease (AD). METHODS: In the Bordeaux-3C prospective cohort, we assessed the impact of herpes simplex virus type 1 (HSV-1) infection on the incidence of AD according to apolipoprotein E (APOE) status, a genetic susceptibility factor. Cox models were performed to estimate the 10-year risk of AD associated with anti-HSV antibodies in 1037 participants according to APOE4 status. RESULTS: Among APOE4 carriers, subjects for whom the frequency of HSV-1 reactivation is supposed to be high, that is, immunoglobulin M (IgM) positive or elevated levels of IgG, had an increased risk of AD with adjusted hazard ratios (HRs) of 3.68 (1.08-12.55) and 3.28 (1.19-9.03), respectively. No significant association was found in APOE4-negative subjects. DISCUSSION: These results, in accordance with a solid pathophysiological rationale, suggest a role for HSV-1 in AD development among subjects with a genetic susceptibility factor, the APOE4 allele.