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

Alzheimers Dement. 2020 Jan;16(1):200-208. doi: 10.1002/alz.12008.


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.

Keywords: APOE4; Alzheimer's disease; dementia; genetic susceptibility; herpes virus; prevention.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease* / epidemiology
  • Alzheimer Disease* / genetics
  • Apolipoprotein E4 / genetics*
  • Female
  • Herpes Simplex / epidemiology*
  • Herpesvirus 1, Human / immunology*
  • Humans
  • Immunoglobulin M
  • Male
  • Prospective Studies


  • Apolipoprotein E4
  • Immunoglobulin M