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Research paper
Inflammatory markers in Alzheimer’s disease and mild cognitive impairment: a meta-analysis and systematic review of 170 studies
  1. Xue-Ning Shen1,
  2. Li-Dong Niu1,
  3. Yan-Jiang Wang2,
  4. Xi-Peng Cao3,
  5. Qiang Liu4,
  6. Lan Tan1,
  7. Can Zhang5,
  8. Jin-Tai Yu6
  1. 1 Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
  2. 2 Department of Neurology and Center for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, China
  3. 3 Clinical Research Center, Qingdao Municipal Hospital, Qingdao, China
  4. 4 Chinese Academy of Sciences Key Laboratory of Brain Function and Disease and School of Life Sciences, University of Science and Technology of China, Hefei, China
  5. 5 Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease (MIND), Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA
  6. 6 Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
  1. Correspondence to Professor Jin-Tai Yu, Department of Neurology, Huashan Hospital, Fudan University, Shanghai 200000, China; yu-jintai{at}


Objective 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.

Methods 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.

Results 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.

  • inflammation
  • mild cognitive impairment
  • Alzheimer’s disease
  • peripheral blood
  • cerebrospinal fluid
  • meta

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  • X-NS and L-DN contributed equally.

  • Contributors J-TY conceptualised and designed the study. X-NS and L-DN conducted the study. X-NS, L-DN and J-TY analysed and extracted the data. X-NS, L-DN and J-TY wrote the first draft of the manuscript. All authors reviewed the manuscript.

  • Funding This work was supported by grants from the National Key R&D Program of China (2018YFC1314700), the National Natural Science Foundation of China (81471309, 81571245, 81501103 and 81701253), Taishan Scholars Program of Shandong Province (ts201511109, tsqn20161078 and tsqn20161079), Qingdao Key Health Discipline Development Fund, and Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders.

  • Competing interests None declared.

  • Patient consent Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.