Abstract
ObjectiveHerpes 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.MethodsThe 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 Aβ1–40 and Aβ1–42 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.ResultsAfter adjustment for study center, age, sex, education, and apolipoprotein E-e4 polymorphism, plasma Aβ1–42 and Aβ1–40 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 Aβ1–42 and β = −132.7, P = 0.002 for Aβ1–40; adjustment for CLU rs2279590, β = −25.6, P = 0.002 for Aβ1–42 and β = −134.8, P = 0.002 for Aβ1–40). No association between the plasma Aβ1–42-to-Aβ1–40 ratio and anti-HSV IgM or IgG were evidenced.ConclusionHigh anti-HSV IgM levels, markers of HSV reactivation, are associated with lower plasma Aβ1–40 and Aβ1–42 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.
Highlights
Previous researches have suggested that Herpes Simplex Virus (HSV), notably type 1 (HSV-1), may constitute a risk factor of Alzheimer’s disease (AD) [1,2,3,4]
These results suggest that a recent reactivation of HSV, characterized by the specific association with anti-HSV IgM antibodies, may be involved in the long-term neuropathological processes leading to dementia [5]
We have previously reported that an increased Ab1–42-to-Ab1–40 plasma ratio was strongly negatively associated with the risk of dementia 2 years later in the Three-City population-based cohort, suggesting that changes in plasma Ab1–40 and Ab1–42 levels might be considered an indicator of short-term risk of dementia [7]
Summary
Previous researches have suggested that Herpes Simplex Virus (HSV), notably type 1 (HSV-1), may constitute a risk factor of Alzheimer’s disease (AD) [1,2,3,4]. We recently assessed the association between seropositivity to HSV and risk of AD in the PAQUID study and found that elderly subjects who were IgMpositive were more likely to develop dementia within the 7 years while no association was found among IgG-positive subjects [5]. These results suggest that a recent reactivation of HSV, characterized by the specific association with anti-HSV IgM antibodies, may be involved in the long-term neuropathological processes leading to dementia [5]. A meta-analysis of plasma Ab levels in AD suggested that in longitudinal studies these parameters might be predictors of higher rates of progression to AD, and should be further explored as potential biomarkers [8]
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