Herpes simplex infection and the risk of Alzheimer's disease: A nested case-control study

Alzheimers Dement. 2015 Jun;11(6):587-92. doi: 10.1016/j.jalz.2014.07.157. Epub 2014 Oct 7.


Background: Herpes simplex virus (HSV) is thought to play an etiological role in the development of Alzheimer's disease (AD).

Methods: Plasma samples from 360 AD cases (75.3% women, mean age 61.2 years) and 360 age- and sex-matched dementia-free controls, taken on average 9.6 years before AD diagnosis, were analyzed for anti-HSV antibodies (immunoglobulin G, IgG, and immunoglobulin M, IgM) by enzyme-linked immunosorbent assays.

Results: In the complete sample group, the presence of anti-HSV IgG and IgM antibodies did not increase the risk of AD significantly (odds ratio (OR) 1.636, P = .069 and OR 1.368, P = .299, respectively). In cases with 6.6 years or more between plasma sampling and AD diagnosis (n = 270), there was a significant association between presence of anti-HSV IgG antibodies and AD (OR 2.250, P = .019).

Conclusion: Among persons with a follow-up time of 6.6 years or more, HSV infection was significantly associated with AD.

Keywords: Alzheimer's disease; Dementia; HSV; Herpes; Herpes simplex; Nested case-control study.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / blood*
  • Alzheimer Disease / epidemiology*
  • Antibodies, Viral / blood
  • Case-Control Studies
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Follow-Up Studies
  • Herpes Simplex / blood*
  • Herpes Simplex / epidemiology*
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin M / blood
  • Logistic Models
  • Male
  • Middle Aged
  • Risk
  • Simplexvirus / immunology


  • Antibodies, Viral
  • Immunoglobulin G
  • Immunoglobulin M