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

Letenneur L, Pérès K, Fleury H, Garrigue I, Barberger-Gateau P, Helmer C, Orgogozo JM, Gauthier S, Dartigues JF - PLoS ONE (2008)

Bottom Line: 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.Reactivation of HSV seropositivity is highly correlated with incident AD.

View Article: PubMed Central - PubMed

Affiliation: INSERM, U897, Bordeaux, France. luc.letenneur@inserm.fr

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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Related in: MedlinePlus

Cumulative Alzheimer's disease rate according to anti-HSV IgG (top) or anti-HSV IgM (bottom) status.Kaplan-Meier estimates, PAQUID study, n = 512.
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pone-0003637-g001: Cumulative Alzheimer's disease rate according to anti-HSV IgG (top) or anti-HSV IgM (bottom) status.Kaplan-Meier estimates, PAQUID study, n = 512.

Mentions: During the follow-up, 69 (16.3%) of the 424 IgG-positive subjects, and 8 (9.1%) of the 88 IgG negative subjects developed AD. Among IgG-positive subjects, mean IgG titres were not significantly different between non-demented and demented subjects (mean (sd) :141 (57.3) and 151 (58.0), respectively, p = 0.13 ; median : 143 and 151 IU/ml, respectively). Thirteen (30.2%) of the 43 IgM-positive and 64 (13.7%) of the 469 IgM-negative subjects developed AD. The cumulative AD rate curves according to IgG and IgM status are displayed in figure 1. HSV-positive subjects showed a greater cumulative probability of developing AD than HSV-negative ones for both IgG and IgM. Cumulative AD rates were about 25% (95% CI: 0.08–0.39) in IgM positive subjects after 10 years of follow-up and reached a frequency of more than 50% (95% CI: 0.33–0.76) after 14 years.


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

Letenneur L, Pérès K, Fleury H, Garrigue I, Barberger-Gateau P, Helmer C, Orgogozo JM, Gauthier S, Dartigues JF - PLoS ONE (2008)

Cumulative Alzheimer's disease rate according to anti-HSV IgG (top) or anti-HSV IgM (bottom) status.Kaplan-Meier estimates, PAQUID study, n = 512.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2572852&req=5

pone-0003637-g001: Cumulative Alzheimer's disease rate according to anti-HSV IgG (top) or anti-HSV IgM (bottom) status.Kaplan-Meier estimates, PAQUID study, n = 512.
Mentions: During the follow-up, 69 (16.3%) of the 424 IgG-positive subjects, and 8 (9.1%) of the 88 IgG negative subjects developed AD. Among IgG-positive subjects, mean IgG titres were not significantly different between non-demented and demented subjects (mean (sd) :141 (57.3) and 151 (58.0), respectively, p = 0.13 ; median : 143 and 151 IU/ml, respectively). Thirteen (30.2%) of the 43 IgM-positive and 64 (13.7%) of the 469 IgM-negative subjects developed AD. The cumulative AD rate curves according to IgG and IgM status are displayed in figure 1. HSV-positive subjects showed a greater cumulative probability of developing AD than HSV-negative ones for both IgG and IgM. Cumulative AD rates were about 25% (95% CI: 0.08–0.39) in IgM positive subjects after 10 years of follow-up and reached a frequency of more than 50% (95% CI: 0.33–0.76) after 14 years.

Bottom Line: 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.Reactivation of HSV seropositivity is highly correlated with incident AD.

View Article: PubMed Central - PubMed

Affiliation: INSERM, U897, Bordeaux, France. luc.letenneur@inserm.fr

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.

Show MeSH
Related in: MedlinePlus