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Cited by 252Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchHerpesvirus Infections and Treatments

Seropositivity to herpes simplex virus antibodies and risk of Alzheimer’s disease: a population-based cohort study

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Letenneur, Luc, Pérès, Karine, Fleury, Hervé, Garrigue, Isabelle, Barberger-Gateau, Pascale, Helmer, Catherine, Orgogozo, Jean-Marc, Gauthier, Serge +1 more·2008·PLoS ONE
DOI 10.1371/journal.pone.0003637PMC PMC2572852
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Abstract

BACKGROUND: Herpes Simplex Virus (HSV) infection has been proposed as a possible risk factor of Alzheimer's Disease (AD) notably because it is neurotropic, ubiquitous in the general population and able to establish lifelong latency in the host. The fact that HSV was present in elderly subjects with AD suggests that the virus could be a co-factor of the disease. We investigated the risk of developing AD in anti-HSV immunoglobulin G (IgG) positive subjects (indicator of a lifelong infection to HSV) and IgM-positive subjects (indicator of primary infection or reactivation of the virus) in a longitudinal population-based cohort of elderly subjects living in the community. METHODS: Cox proportional hazard models were used to study the risk of developing AD according to the presence or not of anti-HSV IgG and IgM antibodies, assessed in the sera of 512 elderly initially free of dementia followed for 14 years. RESULTS: During the follow-up, 77 incident AD cases were diagnosed. Controlled for age, gender, educational level and Apolipoprotein E4 (APOE4) status, IgM-positive subjects showed a significant higher risk of developing AD (HR = 2.55; 95% CI [1.38-4.72]), although no significant increased risk was observed in IgG-positive subjects (HR = 1.67; 95%CI [0.75-3.73]). No modification effect with APOE4 status was found. CONCLUSION: Reactivation of HSV seropositivity is highly correlated with incident AD. HSV chronic infection may therefore be contributive to the progressive brain damage characteristic of AD.

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  • Several studies have failed to detect a relationship between HSV-1 seropositivity/titers and AD/cognitive functioning.

    “Additionally, several studies have failed to detect a relationship between HSV-1 seropositivity/titers and AD/cognitive functioning [30,31].”

    From What would it take to prove that a chronic infection is a causal agent in Alzheimer’s disease? (2025) · cites this paper as [30]

    The Results and Discussion report no significant association between anti-HSV IgG positivity or titres and Alzheimer’s disease, and the Discussion reports another study’s null finding for HSV-1 IgG antibody levels and cognitive decline. However, this cohort did not determine HSV subtype, and it found an increased Alzheimer’s risk for IgM-positive subjects; the claim needs those qualifications. (LLM, conf=0.85)

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References 32 · Cited by 252

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Authors
Letenneur, L., Pérès, K., Fleury, H., Garrigue, I., Barberger-Gateau, P., Helmer, C., Orgogozo, J.-M., Gauthier, S., & Dartigues, J.-F.
Affiliations
  • Inserm (FR)
  • Université Bordeaux Segalen (FR)
  • McGill University Research Centre for Studies in Aging (CA)
Corresponding author
Letenneur, Luc
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2008-11-04
Volume
3
Issue
11
Pages
e3637
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0003637
PMC
PMC2572852
OpenAlex
W2026589693
Cited by
252
References
32
Citations by year
2026: 14 · 2025: 16 · 2024: 11 · 2023: 10 · 2022: 32 · 2021: 29 · 2020: 22 · 2019: 14 · 2018: 14 · 2017: 7 · 2016: 11 · 2015: 9 · 2014: 17 · 2013: 13 · 2012: 8
FWCI
5.66
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Fondation de France
  • Ipsen
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Epidemiology › Herpesvirus Infections and Treatments
Keywords
herpes simplex virus, Alzheimer's disease, viral reactivation, chronic viral infection, APOE ε4, dementia risk, older adults, neurodegeneration
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Antibodies, Viral, Female, Herpes Simplex, Humans, Immunoglobulin G, Male, Middle Aged, Risk Factors, Proportional Hazards Models, Seroepidemiologic Studies, Simplexvirus

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