INTRATHECAL ANTIBODIES AGAINST HERPES SIMPLEX VIRUS ARE ASSOCIATED WITH TAU PATHOLOGY IN HUMANS WITH ALZHEIMER’S DISEASE
- Oliver Goldhardt, Germany
Abstract
Aims
Recurrent infection with herpes simplex virus type 1 (HSV1) has been discussed as contributing to Alzheimer’s disease (AD) pathology. HSV1 triggers beta-amyloid (Aβ) accumulation and tau pathology in cell culture and animal models. Aβ limits the activity of the virus. In humans, HSV1 seropositivity in particular with parallel cytomegalovirus (CMV) seropositivity increases the risk for AD. In this study, the associations of serological HSV and CMV biomarkers with CSF AD biomarkers in humans with AD and cognitively normal controls (NC) were investigated.
Methods
In 82 patients with AD and 30 NCs, total Tau (tTau), pTau, Aβ42 and Aβ40 were measured in CSF. All patients were positive for amyloid pathology (amyloid PET or CSF-Aβ42/Aβ40 ratio). CSF to serum anti-HSV1/2-IgG and anti-CMV-IgG antibody index (AI-IgGHSV1/2 and AI-IgGCMV) were determined by ELISA. In HSV1-or CMV-seropositives, associations between HSV-AI, or CMV-AI, and CSF AD biomarkers were investigated by linear regression models controlled for APOE genotype, sex and age.
Results
CSF-pTau was significantly and positively predicted by AI-IgGHSV1/2 and negatively by the CSF-Aβ42/Aβ40 ratio in HSV1-seropositive patients with AD, both in univariate and multivariate analyses. Furthermore, a significant and negative interaction between the AI-IgGHSV1/2 and CSF-Aβ42/Aβ40 ratio on pTau was found. AI-IgGCMV was not significantly associated with AD biomarkers. In healthy controls no associations were identified between viral AI and AD biomarkers.
Conclusions
The results support the hypothesis of a specific effect of HSV on AD pathology.