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.


CONCLUSIONS
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.
INSERM, U897, Bordeaux, France. catherine.feart@isped.u-bordeaux2.fr
Catherine
C
Féart
Catherine
C
Helmer
Hervé
H
Fleury
Yannick
Y
Béjot
Karen
K
Ritchie
Philippe
P
Amouyel
Susanna
S
Schraen-Maschke
Luc
L
Buée
Jean-Charles
JC
Lambert
Luc
L
Letenneur
Jean-François
JF
Dartigues
D000368:Aged; D016229:Amyloid beta-Peptides / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology*; D008297:Male; D010446:Peptide Fragments / Q000097:blood*; D018139:Simplexvirus / Q000276:immunology*; D014775:Virus Activation
D016229:Amyloid beta-Peptides; D007075:Immunoglobulin M; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)