PMID- 30630955
OWN - NLM
STAT- MEDLINE
DCOM- 20200319
LR  - 20200319
IS  - 1468-330X (Electronic)
IS  - 0022-3050 (Linking)
VI  - 90
IP  - 5
DP  - 2019 May
TI  - Inflammatory markers in Alzheimer's disease and mild cognitive impairment: a 
      meta-analysis and systematic review of 170 studies.
PG  - 590-598
LID - 10.1136/jnnp-2018-319148 [doi]
AB  - 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 (alpha1-ACT) (1.217, p<0.005), IL-1beta (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), alpha1-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.
CI  - (c) Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and 
      permissions. Published by BMJ.
FAU - Shen, Xue-Ning
AU  - Shen XN
AD  - Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, 
      China.
FAU - Niu, Li-Dong
AU  - Niu LD
AD  - Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, 
      China.
FAU - Wang, Yan-Jiang
AU  - Wang YJ
AD  - Department of Neurology and Center for Clinical Neuroscience, Daping Hospital, 
      Third Military Medical University, Chongqing, China.
FAU - Cao, Xi-Peng
AU  - Cao XP
AD  - Clinical Research Center, Qingdao Municipal Hospital, Qingdao, China.
FAU - Liu, Qiang
AU  - Liu Q
AD  - 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.
FAU - Tan, Lan
AU  - Tan L
AD  - Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, 
      China.
FAU - Zhang, Can
AU  - Zhang C
AD  - Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative 
      Disease (MIND), Department of Neurology, Massachusetts General Hospital, Harvard 
      Medical School, Charlestown, Massachusetts, USA.
FAU - Yu, Jin-Tai
AU  - Yu JT
AD  - Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai 
      Medical College, Fudan University, Shanghai, China yu-jintai@163.com.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
PT  - Systematic Review
DEP - 20190110
PL  - England
TA  - J Neurol Neurosurg Psychiatry
JT  - Journal of neurology, neurosurgery, and psychiatry
JID - 2985191R
RN  - 0 (Biomarkers)
SB  - IM
MH  - Alzheimer Disease/*metabolism
MH  - Biomarkers/metabolism
MH  - Cognitive Dysfunction/*metabolism
MH  - Humans
MH  - Inflammation/*metabolism
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - cerebrospinal fluid
OT  - inflammation
OT  - meta
OT  - mild cognitive impairment
OT  - peripheral blood
COIS- Competing interests: None declared.
EDAT- 2019/01/12 06:00
MHDA- 2020/03/20 06:00
CRDT- 2019/01/12 06:00
PHST- 2018/07/02 00:00 [received]
PHST- 2018/11/05 00:00 [revised]
PHST- 2018/12/10 00:00 [accepted]
PHST- 2019/01/12 06:00 [pubmed]
PHST- 2020/03/20 06:00 [medline]
PHST- 2019/01/12 06:00 [entrez]
AID - jnnp-2018-319148 [pii]
AID - 10.1136/jnnp-2018-319148 [doi]
PST - ppublish
SO  - J Neurol Neurosurg Psychiatry. 2019 May;90(5):590-598. doi: 
      10.1136/jnnp-2018-319148. Epub 2019 Jan 10.