Inflammatory markers in Alzheimer’s disease and mild cognitive impairment: a meta-analysis and systematic review of 170 studies

• Published in: Journal of neurology, neurosurgery and psychiatry Vol. 90; no. 5; pp. 590 - 598
• Main Authors: Shen, Xue-Ning, Niu, Li-Dong, Wang, Yan-Jiang, Cao, Xi-Peng, Liu, Qiang, Tan, Lan, Zhang, Can, Yu, Jin-Tai
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd 01.05.2019; BMJ Publishing Group LTD
• Subjects: Alzheimer Disease - metabolism; Alzheimer's disease; Biomarkers - metabolism; Brain research; Cerebrospinal fluid; Chitinase; Cognition & reasoning; Cognitive ability; Cognitive Dysfunction - metabolism; Cognitive neurology; Cytokines; Dementia; Humans; Inflammation; Inflammation - metabolism; meta; Meta-analysis; mild cognitive impairment; peripheral blood; Plasma; Proteins; Sample size; Statistical analysis; Studies; Systematic review; TNF inhibitors; Tumor necrosis factor-TNF; mild cognitive impairment; peripheral blood; Alzheimer’s disease; inflammation; meta; cerebrospinal fluid
• DOI: 10.1136/jnnp-2018-319148
• ISSN: 0022-3050; 1468-330X

ObjectiveInflammation 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.MethodsStudies 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.ResultsA 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.ConclusionSignificantly 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.