Seropositivity to Herpes Simplex Virus Antibodies and Risk of Alzheimers Disease A Population-Based Cohort Study 英文参考文献.docVIP

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Seropositivity to Herpes Simplex Virus Antibodies and Risk of Alzheimers Disease A Population-Based Cohort Study 英文参考文献.doc

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Seropositivity to Herpes Simplex Virus Antibodies and Risk of Alzheimers Disease A Population-Based Cohort Study 英文参考文献

SeropositivitytoHerpesSimplexVirusAntibodiesand RiskofAlzheimer’sDisease:APopulation-BasedCohort Study LucLetenneur1,2*,KarinePe′re`s1,2,Herve′ Fleury2,3,IsabelleGarrigue2,3,PascaleBarberger-Gateau1,2 , CatherineHelmer1,2,Jean-MarcOrgogozo1,2,SergeGauthier4,Jean-Franc?oisDartigues1,2 1INSERM,U897,Bordeaux,France,2UniversiteVictorSegalenBordeaux2,Bordeaux,France,3UniversiteVictorSegalenBordeaux2,LaboratoiredeVirologie,Bordeaux, France,4McGillUniversity,CentreforStudiesinAging,Montreal,Quebec,Canada Abstract Background:HerpesSimplexVirus(HSV)infectionhasbeenproposedasapossibleriskfactorofAlzheimer’sDisease(AD) notablybecauseitisneurotropic,ubiquitousinthegeneralpopulationandabletoestablishlifelonglatencyinthehost.The fact that HSV was present in elderly subjects with AD suggests that the virus could be a co-factor of the disease. We investigatedtheriskofdevelopingADinanti-HSVimmunoglobulinG(IgG)positivesubjects(indicatorofalifelonginfection toHSV)andIgM-positivesubjects(indicatorofprimaryinfectionorreactivationofthevirus)inalongitudinalpopulation- basedcohortofelderlysubjectslivinginthecommunity. Methods:CoxproportionalhazardmodelswereusedtostudytheriskofdevelopingADaccordingtothepresenceornotof anti-HSVIgGandIgMantibodies,assessedintheseraof512elderlyinitiallyfreeofdementiafollowedfor14years. Results: During the follow-up, 77 incident AD cases were diagnosed. Controlled for age, gender, educational level and ApolipoproteinE4(APOE4)status,IgM-positivesubjectsshowedasignificanthigherriskofdevelopingAD(HR=2.55;95% CI[1.38–4.72]),althoughnosignificantincreasedriskwasobservedinIgG-positivesubjects(HR=1.67;95%CI[0.75–3.73]). NomodificationeffectwithAPOE4statuswasfound. Conclusion:ReactivationofHSVseropositivityishighlycorrelatedwithincidentAD.HSVchronicinfectionmaythereforebe contributivetotheprogressivebraindamagecharacteristicofAD. Citation:LetenneurL,Pe′re`sK,FleuryH,GarrigueI,Barberger-GateauP,etal.(2008)SeropositivitytoHerpesSimplexVirusAntibodiesandRiskofAlzheim