Abstract
BackgroundHerpes 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.MethodsCox 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.ResultsDuring 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.ConclusionReactivation of HSV seropositivity is highly correlated with incident AD. HSV chronic infection may therefore be contributive to the progressive brain damage characteristic of AD.
Highlights
In the general population, Herpes Simplex Virus (HSV) is highly prevalent [1,2,3]
On the basis of this hippocampal and temporal tropism of the virus, HSV was proposed as a candidate environmental risk factor for Alzheimer’s Disease (AD) [5]
Some studies found that HSV has been detected in the brain of many AD patients, both by direct detection of virus DNA by polymerase chain reaction (PCR) [6] and by the detection of intrathecal antibodies [7]
Summary
Herpes Simplex Virus (HSV) is highly prevalent (more than 70% after age 50) [1,2,3]. Herpes Simplex Encephalopathy (HSE) is a rare but very severe acute infection of the central nervous system [4] It has a very different course from Alzheimer’s disease (AD), it leads to the occurrence of bilateral hippocampal-inner temporal lesions resulting in profound verbal memory loss, characteristic of AD. 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. 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 populationbased cohort of elderly subjects living in the community
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