Association between IgM anti-herpes simplex virus and plasma amyloid-beta levels

Abstract

Objective: Herpes simplex virus (HSV) reactivation has been identified as a possible risk factor for Alzheimer's disease (AD) and plasma amyloid-beta (Aβ) levels might be considered as possible biomarkers of the risk of AD. The aim of our study was to investigate the association between anti-HSV antibodies and plasma Aβ levels. Methods: The study sample consisted of 1222 subjects (73.9 y in mean) from the Three-City cohort. IgM and IgG anti-HSV antibodies were quantified using an ELISA kit, and plasma levels of Aβ 1-40 and Aβ 1-42 were measured using an xMAP-based assay technology. Cross-sectional analyses of the associations between anti-HSV antibodies and plasma Aβ levels were performed by multi-linear regression. Results: After adjustment for study center, age, sex, education, and apolipoprotein E-e4 polymorphism, plasma Aβ 1-42 and Aβ 1-40 levels were specifically inversely associated with anti-HSV IgM levels (β = -20.7, P = 0.001 and β = -92.4, P = 0.007, respectively). In a sub-sample with information on CLU- and CR1-linked SNPs genotyping (n = 754), additional adjustment for CR1 or CLU markers did not modify these associations (adjustment for CR1 rs6656401, β = -25.6, P = 0.002 for Aβ 1-42 and β = -132.7, P = 0.002 for Aβ 1-40; adjustment for CLU rs2279590, β = -25.6, P = 0.002 for Aβ 1-42 and β = -134.8, P = 0.002 for Aβ 1-40). No association between the plasma Aβ 1-42-to-Aβ 1-40 ratio and anti-HSV IgM or IgG were evidenced. Conclusion: High anti-HSV IgM levels, markers of HSV reactivation, are associated with lower plasma Aβ 1-40 and Aβ 1-42 levels, which suggest a possible involvement of the virus in the alterations of the APP processing and potentially in the pathogenesis of AD in human. © 2011 Féart et al.