Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China.
Department of Neurology and Center for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, China.
J Neurol Neurosurg Psychiatry. 2019 May;90(5):590-598. doi: 10.1136/jnnp-2018-319148. Epub 2019 Jan 10.
Inflammation plays a crucial role in the pathogenesis of mild cognitive impairment (MCI) and Alzheimer's disease (AD). Our study aimed to analyse previous inconsistent results of inflammatory markers in AD and MCI quantitatively.
Studies reporting concentrations of peripheral or cerebrospinal fluid (CSF) markers were included, and eligible data on AD, MCI and control were extracted. Pooled Hedges's g was adopted to illustrate comparisons, and various confounding factors were used to explore sources of heterogeneity.
A total of 170 studies were included in the meta-analysis and systematic review, which demonstrated increased peripheral levels of high-sensitivity C reactive protein (Hedges's g 0.281, p<0.05), interleukin-6 (IL-6) (0.429, p<0.005), soluble tumour necrosis factor receptor 1 (sTNFR1) (0.763, p<0.05), soluble tumour necrosis factor receptor 2 (sTNFR2) (0.354, p<0.005), alpha1-antichymotrypsin (α1-ACT) (1.217, p<0.005), IL-1β (0.615, p<0.05) and soluble CD40 ligand (0.868, p<0.005), and CSF levels of IL-10 (0.434, p<0.05), monocyte chemoattractant protein-1 (MCP-1) (0.798, p<0.005), transforming growth factor-beta 1 (1.009, p<0.05), soluble triggering receptor expressed on myeloid cells2 (sTREM2) (0.587, p<0.001), YKL-40 (0.849, p<0.001), α1-ACT (0.638, p<0.001), nerve growth factor (5.475, p<0.005) and visinin-like protein-1 (VILIP-1) (0.677, p<0.005), in AD compared with the control. Higher levels of sTNFR2 (0.265, p<0.05), IL-6 (0.129, p<0.05) and MCP-1 (0.779, p<0.05) and lower levels of IL-8 (-1.293, p<0.05) in the periphery, as well as elevated concentrations of YKL-40 (0.373, p<0.05), VILIP-1 (0.534, p<0.005) and sTREM2 (0.695, p<0.05) in CSF, were shown in MCI compared with the control. Additionally, increased peripheral sTNFR1 (0.582, p<0.05) and sTNFR2 (0.254, p<0.05) levels were observed in AD compared with MCI.
Significantly altered levels of inflammatory markers were verified in comparison between AD, MCI and control, supporting the notion that AD and MCI are accompanied by inflammatory responses in both the periphery and CSF.
炎症在轻度认知障碍（MCI）和阿尔茨海默病（AD）的发病机制中起着至关重要的作用。我们的研究旨在定量分析 AD 和 MCI 中炎症标志物的先前不一致结果。
纳入了报告外周或脑脊液（CSF）标志物浓度的研究，并提取了 AD、MCI 和对照组的合格数据。采用合并 Hedges's g 来说明比较，并用各种混杂因素来探索异质性的来源。
共有 170 项研究纳入了荟萃分析和系统评价，结果表明外周高敏 C 反应蛋白（Hedges's g 0.281，p<0.05）、白细胞介素-6（IL-6）（0.429，p<0.005）、可溶性肿瘤坏死因子受体 1（sTNFR1）（0.763，p<0.05）、可溶性肿瘤坏死因子受体 2（sTNFR2）（0.354，p<0.005）、α1-抗糜蛋白酶（α1-ACT）（1.217，p<0.005）、IL-1β（0.615，p<0.05）和可溶性 CD40 配体（0.868，p<0.005）水平升高，CSF 中白细胞介素-10（IL-10）（0.434，p<0.05）、单核细胞趋化蛋白-1（MCP-1）（0.798，p<0.005）、转化生长因子-β1（1.009，p<0.05）、髓样细胞触发受体表达的可溶性 2（sTREM2）（0.587，p<0.001）、YKL-40（0.849，p<0.001）、α1-ACT（0.638，p<0.001）、神经生长因子（5.475，p<0.005）和视黄醇结合蛋白 1（VILIP-1）（0.677，p<0.001）在 AD 与对照组相比升高。外周 sTNFR2（0.265，p<0.05）、IL-6（0.129，p<0.05）和 MCP-1（0.779，p<0.05）水平升高，IL-8（-1.293，p<0.05）水平降低，CSF 中 YKL-40（0.373，p<0.05）、VILIP-1（0.534，p<0.005）和 sTREM2（0.695，p<0.05）浓度升高，MCI 与对照组相比。此外，AD 与 MCI 相比，外周 sTNFR1（0.582，p<0.05）和 sTNFR2（0.254，p<0.05）水平升高。
AD、MCI 和对照组之间的炎症标志物水平差异显著，支持 AD 和 MCI 在外周和 CSF 中均伴有炎症反应的观点。
