title: Seropositivity to herpes simplex virus antibodies and risk of Alzheimer's disease: a population-based cohort study.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: INSERM, U897, Bordeaux, France. luc.letenneur@inserm.fr
authors.forename: Luc
authors.initials: L
authors.lastname: Letenneur
authors.forename: Karine
authors.initials: K
authors.lastname: Pérès
authors.forename: Hervé
authors.initials: H
authors.lastname: Fleury
authors.forename: Isabelle
authors.initials: I
authors.lastname: Garrigue
authors.forename: Pascale
authors.initials: P
authors.lastname: Barberger-Gateau
authors.forename: Catherine
authors.initials: C
authors.lastname: Helmer
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Orgogozo
authors.forename: Serge
authors.initials: S
authors.lastname: Gauthier
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Dartigues
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000175:diagnosis / Q000821:virology*; D000914:Antibodies, Viral / Q000097:blood*; D005260:Female; D006561:Herpes Simplex / Q000097:blood / Q000473:pathology / Q000821:virology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012307:Risk Factors; D016036:Seroepidemiologic Studies; D018139:Simplexvirus / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D007074:Immunoglobulin G