Association between IgM Anti-Herpes Simplex Virus and Plasma Amyloid-Beta Levels

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

Linkage analysis for plasma amyloid beta levels in persons with hypertension implicates A beta-40 levels to presenilin 2

Item does not contain fulltextPlasma concentrations of Abeta40 and Abeta42 rise with age and are increased in people with mutations that cause early-onset Alzheimer's disease (AD). Amyloid beta (Abeta) plasma levels were successfully used as an (endo)phenotype for gene discovery using a linkage approach in families with dominant forms of disease. Here, we searched for loci involved in Abeta plasma levels in a series of non-demented patients with hypertension in the Erasmus Rucphen Family study. Abeta40 and Abeta42 levels were determined in 125 subjects with severe hypertension. All patients were genotyped with a 6,000 single nucleotide polymorphisms (SNPs) illumina array designed for linkage analysis. We conducted linkage analysis of plasma Abeta levels. None of the linkage analyses yielded genome-wide significant logarithm of odds (LOD) score over 3.3, but there was suggestive evidence for linkage (LOD > 1.9) for two regions: 1q41 (LOD = 2.07) and 11q14.3 (LOD = 2.97), both for Abeta40. These regions were followed up with association analysis in the study subjects and in 320 subjects from a population-based cohort. For the Abeta40 region on chromosome 1, association of several SNPs was observed at the presenilin 2 gene (PSEN2) (p = 2.58 x 10(-4) for rs6703170). On chromosome 11q14-21, we found some association (p = 3.1 x 10(-3) for rs2514299). This linkage study of plasma concentrations of Abeta40 and Abeta42 yielded two suggestive regions, of which one points toward a known locus for familial AD