Herpes simplex virus alters Alzheimer's disease biomarkers ‐ A hypothesis paper
Oliver Goldhardt, Robert H. Freiberger, Tobias Dreyer, Luisa Willner, Igor Yakushev, Marion Ortner, Hans Förstl, Janine Diehl‐Schmid, Esther Milz, Josef Priller, Alfredo Ramı́rez, Viktor Magdolen, Markus Thaler, Timo Grimmer
Abstract
Abstract Introduction Human herpes simplex virus 1 (HSV1) is discussed to induce amyloid‐β (Aβ) accumulation and neurofibrillary tangles of hyperphosphorylated tau (pTau) in Alzheimer's disease (AD) in cell culture and animal models. Aβ appears to be virostatic. We investigated the association between intrathecal antibodies against HSV or cytomegalovirus (CMV) and cerebrospinal fluid (CSF) AD biomarkers. Methods Aβ 42 /Aβ 40 ratio, pTau, and tTau were measured in CSF of 117 patients with early AD positive for amyloid pathology (A+) and 30 healthy controls (A‐). CSF‐to‐serum anti‐HSV1/2‐IgG antibody indices (AI‐IgG HSV1/2 ) and CMV (AI‐IgG CMV ) were determined by enzyme‐linked immunosorbent assay (ELISA). Results Exclusively in HSV1‐seropositive AD, pTau was positively and significantly predicted by AI‐IgG HSV1/2 and negatively by the Aβ 42 /Aβ 40 ratio in both univariate and multivariate regression analyses. Furthermore, a significant and negative interaction between the AI‐IgG HSV1/2 and Aβ 42 /Aβ 40 ratio on pTau was found. Discussion The results support the hypothesis that HSV infection contributes to AD. Highlights HSV antibody index is positively associated with tau pathology in patients with AD. HSV antibody index is negatively associated with cerebral FDG metabolism. Amyloid modulates the association of HSV antibody index with CSF‐pTau. HSV in AD offers a pathophysiological model connecting tau and amyloid.