by Catherine Féart, Catherine Helmer, Hervé Fleury, Yannick Béjot, Karen Ritchie, Philippe Amouyel, Susanna Schraen-Maschke, Luc Buée, Jean-Charles Lambert, Luc Letenneur, Jean-François Dartigues
Herpes simplex virus (HSV) reactivation has been identified as a possible risk factor for Alzheimer's disease (AD) and plasma amyloid-beta (Aß) 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 Aß 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 Aß1–40 and Aß1–42 were measured using an xMAP-based assay technology. Cross-sectional analyses of the associations between anti-HSV antibodies and plasma Aß levels were performed by multi-linear regression. Results
After adjustment for study center, age, sex, education, and apolipoprotein E-e4 polymorphism, plasma Aß1–42 and Aß1–40 levels were specifically inversely associated with anti-HSV IgM levels (ß?=?-20.7, P?=?0.001 and ß?=?-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, ß?=?-25.6, P?=?0.002 for Aß1–42 and ß?=?-132.7, P?=?0.002 for Aß1–40; adjustment for CLU rs2279590, ß?=?-25.6, P?=?0.002 for Aß1–42 and ß?=?-134.8, P?=?0.002 for Aß1–40). No association between the plasma Aß1–42-to-Aß1–40 ratio and anti-HSV IgM or IgG were evidenced. Conclusion
High anti-HSV IgM levels, markers of HSV reactivation, are associated with lower plasma Aß1–40 and Aß1–42 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.