Goldhardt Oliver, Freiberger Robert, Dreyer Tobias, Willner Luisa, Yakushev Igor, Ortner Marion, Förstl Hans, Diehl-Schmid Janine, Milz Esther, Priller Josef, Ramirez Alfredo, Magdolen Viktor, Thaler Markus, Grimmer Timo
Department of Psychiatry and Psychotherapy, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
Department of Obstetrics and Gynecology, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
Alzheimers Dement. 2023 May;19(5):2117-2134. doi: 10.1002/alz.12834. Epub 2022 Nov 17.
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.
Aβ /Aβ 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 ) and CMV (AI-IgG ) were determined by enzyme-linked immunosorbent assay (ELISA).
Exclusively in HSV1-seropositive AD, pTau was positively and significantly predicted by AI-IgG and negatively by the Aβ /Aβ ratio in both univariate and multivariate regression analyses. Furthermore, a significant and negative interaction between the AI-IgG and Aβ /Aβ ratio on pTau was found.
The results support the hypothesis that HSV infection contributes to AD.
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.
在细胞培养和动物模型中，有人讨论过人类单纯疱疹病毒1型（HSV1）会在阿尔茨海默病（AD）中诱导淀粉样β蛋白（Aβ）积累以及过度磷酸化tau蛋白（pTau）的神经原纤维缠结。Aβ似乎具有抗病毒作用。我们研究了鞘内抗HSV或巨细胞病毒（CMV）抗体与脑脊液（CSF）AD生物标志物之间的关联。
在117例淀粉样病变呈阳性（A+）的早期AD患者和30名健康对照者（A-）的脑脊液中测量Aβ/Aβ比值、pTau和总tau蛋白（tTau）。通过酶联免疫吸附测定（ELISA）确定脑脊液与血清抗HSV1/2-IgG抗体指数（AI-IgG）和CMV（AI-IgG）。
仅在HSV1血清学阳性的AD患者中，在单变量和多变量回归分析中，AI-IgG可正向且显著预测pTau，而Aβ/Aβ比值则呈负向预测。此外，发现AI-IgG与Aβ/Aβ比值对pTau存在显著的负向相互作用。
结果支持HSV感染导致AD的假说。
AD患者中HSV抗体指数与tau病理呈正相关。HSV抗体指数与脑FDG代谢呈负相关。淀粉样蛋白调节HSV抗体指数与脑脊液pTau之间的关联。AD中的HSV提供了一个连接tau和淀粉样蛋白的病理生理模型。
