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Inflammatory markers in Alzheimer's disease and mild cognitive impairment: A meta‐analysis and systematic review of 170 studies
Author(s) -
Shen XueNing,
Niu LiDong,
Wang Yanjiang,
Cao XiPeng,
Liu Qiang,
Tan Lan,
Zhang Can,
Yu JinTai
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.041476
Subject(s) - confounding , medicine , pathogenesis , receptor , inflammation , cerebrospinal fluid , meta analysis , interleukin 6 , cognitive impairment , tumor necrosis factor alpha , disease , gastroenterology , endocrinology
Background 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. Method 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. Result 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. Conclusion 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.