Department of Neurosciences, Centro Hospitalar do Porto, Porto, Portugal; Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga, Guimarães, Portugal.
Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga, Guimarães, Portugal.
Neurobiol Aging. 2019 Apr;76:125-132. doi: 10.1016/j.neurobiolaging.2018.12.019. Epub 2019 Jan 7.
Cumulative data suggest that neuroinflammation plays a prominent role in Alzheimer's disease (AD) pathogenesis. The purpose of this work was to assess if patients with AD present a specific cerebrospinal fluid (CSF) cytokine profile and if it correlates to disease progression. We determined the levels of 27 cytokines in CSF of patients with AD and compared them with patients with frontotemporal dementia and nondemented controls. In addition, we correlated the cytokine levels with cognitive status and disease progression after 12 months. Patients with AD had higher levels of proinflammatory and anti-inflammatory cytokines (eotaxin, interleukin [IL]-1ra, IL-4, IL-7, IL-8, IL-9, IL-10, IL-15, granulocyte colony-stimulating factor, monocyte chemotactic protein 1, platelet-derived growth factor, tumor necrosis factor alfa) compared to nondemented controls. There was a negative correlation between the disease progression and the levels of several cytokines (IL-1β, IL-4, IL-6, IL-9, IL-17A, basic fibroblast growth factor, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interferon gamma, macrophage inflammatory proteins-1β). To the best of our knowledge, this is the first study reporting a "protective" role of the upregulation of specific intrathecal cytokine levels in AD. This finding supports that a fine "rebalancing" of the immune system represents a new target in AD therapeutic approach.
累积数据表明神经炎症在阿尔茨海默病（AD）发病机制中起着重要作用。本研究旨在评估 AD 患者是否存在特定的脑脊液（CSF）细胞因子谱，以及该谱是否与疾病进展相关。我们测定了 AD 患者 CSF 中 27 种细胞因子的水平，并与额颞叶痴呆患者和非痴呆对照组进行了比较。此外，我们还将细胞因子水平与认知状态和 12 个月后的疾病进展相关联。与非痴呆对照组相比，AD 患者的促炎和抗炎细胞因子（嗜酸性粒细胞趋化因子、白细胞介素-1 受体拮抗剂、白细胞介素-4、白细胞介素-7、白细胞介素-8、白细胞介素-9、白细胞介素-10、白细胞介素-15、粒细胞集落刺激因子、单核细胞趋化蛋白-1、血小板衍生生长因子、肿瘤坏死因子-α）水平更高。细胞因子水平与疾病进展呈负相关（白细胞介素-1β、白细胞介素-4、白细胞介素-6、白细胞介素-9、白细胞介素-17A、碱性成纤维细胞生长因子、粒细胞集落刺激因子、粒细胞-巨噬细胞集落刺激因子、干扰素-γ、巨噬细胞炎性蛋白-1β）。据我们所知，这是第一项报道 AD 患者特定鞘内细胞因子水平上调具有“保护”作用的研究。这一发现支持了免疫系统的精细“再平衡”是 AD 治疗方法的新靶点。
