Morgane Linard1, Luc Letenneur1, Isabelle Garrigue2, Angélique Doize2, Jean-François Dartigues1, Catherine Helmer1,3. 1. INSERM, Bordeaux Population Health Research Center, University of Bordeaux, UMR U1219, Bordeaux, France. 2. CNRS-UMR 5234 and CHU Bordeaux, Virology Department, University of Bordeaux, Bordeaux, France. 3. CIC1401-EC, Center for Clinical Investigation-Clinical Epidemiology, F-33000, Bordeaux, France.
Abstract
INTRODUCTION: Numerous results suggest the implication of infectious agents in the onset of Alzheimer's disease (AD). METHODS: In the Bordeaux-3C prospective cohort, we assessed the impact of herpes simplex virus type 1 (HSV-1) infection on the incidence of AD according to apolipoprotein E (APOE) status, a genetic susceptibility factor. Cox models were performed to estimate the 10-year risk of AD associated with anti-HSV antibodies in 1037 participants according to APOE4 status. RESULTS: Among APOE4 carriers, subjects for whom the frequency of HSV-1 reactivation is supposed to be high, that is, immunoglobulin M (IgM) positive or elevated levels of IgG, had an increased risk of AD with adjusted hazard ratios (HRs) of 3.68 (1.08-12.55) and 3.28 (1.19-9.03), respectively. No significant association was found in APOE4-negative subjects. DISCUSSION: These results, in accordance with a solid pathophysiological rationale, suggest a role for HSV-1 in AD development among subjects with a genetic susceptibility factor, the APOE4 allele.
INTRODUCTION: Numerous results suggest the implication of infectious agents in the onset of Alzheimer's disease (AD). METHODS: In the Bordeaux-3C prospective cohort, we assessed the impact of herpes simplex virus type 1 (HSV-1) infection on the incidence of AD according to apolipoprotein E (APOE) status, a genetic susceptibility factor. Cox models were performed to estimate the 10-year risk of AD associated with anti-HSV antibodies in 1037 participants according to APOE4 status. RESULTS: Among APOE4 carriers, subjects for whom the frequency of HSV-1 reactivation is supposed to be high, that is, immunoglobulin M (IgM) positive or elevated levels of IgG, had an increased risk of AD with adjusted hazard ratios (HRs) of 3.68 (1.08-12.55) and 3.28 (1.19-9.03), respectively. No significant association was found in APOE4-negative subjects. DISCUSSION: These results, in accordance with a solid pathophysiological rationale, suggest a role for HSV-1 in AD development among subjects with a genetic susceptibility factor, the APOE4 allele.
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