Department of Infectious Diseases, University of Gothenburg, Gothenburg, Sweden.
J Neurol. 2013 Feb;260(2):620-6. doi: 10.1007/s00415-012-6688-y. Epub 2012 Oct 9.
The cerebrospinal fluid (CSF) biomarker profile in Alzheimer's disease (AD) is characterized by decreased beta amyloid (Aβ(1-42)), increased total and hyperphosphorylated tau (t-tau and p-tau, respectively), which is a useful diagnostic tool and gives insight in the pathogenesis of AD. It is of importance to study how these biomarkers react in other CNS diseases; therefore, we decided to analyse amyloid and tau biomarkers in different CNS infections. We also included analysis of soluble amyloid precursor proteins (sAPPα and -β). CSF Aβ(1-42), sAPPα and -β, t-tau and p-tau were analysed in bacterial meningitis (n = 12), Lyme neuroborreliosis (n = 13), herpes simplex virus type 1 (HSV-1) encephalitis (n = 10), HIV-associated dementia (HAD) (n = 21), AD (n = 21) and healthy controls (n = 42). Concurrent with AD, Aβ(1-42) was decreased in all groups except neuroborreliosis compared to controls. HSV-1 encephalitis, bacterial meningitis and HAD showed lower concentrations of sAPPα and -β compared to AD. T-tau was increased in AD and HSV-1 encephalitis compared to all other groups. P-tau was higher in AD and HSV-1 encephalitis compared to bacterial meningitis, HAD and control. Decreased CSF Aβ(1-42), sAPPα and -β in various CNS infections imply an effect of neuroinflammation on amyloid metabolism which is similar in regard to AD concerning Aβ(1-42), but differs concerning sAPPα and -β. These results clearly indicate different pathologic pathways in AD and infectious CNS disease and may provide help in the differential biomarker diagnostics. Increased p-tau in HSV-1 encephalitis probably reflect acute neuronal damage and necrosis.
阿尔茨海默病（AD）患者的脑脊液（CSF）生物标志物特征为β淀粉样蛋白（Aβ（1-42））减少，总tau 和磷酸化 tau（t-tau 和 p-tau）增加，这是一种有用的诊断工具，可以深入了解 AD 的发病机制。研究这些生物标志物在其他中枢神经系统疾病中的反应非常重要；因此，我们决定分析不同中枢神经系统感染中的淀粉样蛋白和 tau 生物标志物。我们还包括对可溶性淀粉样前体蛋白（sAPPα 和 -β）的分析。我们分析了细菌性脑膜炎（n = 12）、莱姆神经Borreliosis（n = 13）、单纯疱疹病毒 1 型（HSV-1）脑炎（n = 10）、艾滋病毒相关痴呆（HAD）（n = 21）、AD（n = 21）和健康对照组（n = 42）的 CSF Aβ（1-42）、sAPPα 和 -β、t-tau 和 p-tau。与 AD 并发，除神经Borreliosis 外，所有组的 Aβ（1-42）均低于对照组。与 AD 相比，HSV-1 脑炎、细菌性脑膜炎和 HAD 显示出较低的 sAPPα 和 -β 浓度。与其他所有组相比，AD 和 HSV-1 脑炎的 t-tau 增加。与细菌性脑膜炎、HAD 和对照组相比，AD 和 HSV-1 脑炎的 p-tau 更高。各种中枢神经系统感染中 CSF Aβ（1-42）、sAPPα 和 -β 的减少表明神经炎症对淀粉样蛋白代谢有影响，这与 AD 关于 Aβ（1-42）相似，但与 sAPPα 和 -β 不同。这些结果清楚地表明 AD 和感染性中枢神经系统疾病的不同病理途径，并可能有助于鉴别生物标志物诊断。HSV-1 脑炎中 p-tau 的增加可能反映了急性神经元损伤和坏死。
