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Cerebrospinal Fluid Inflammatory Cytokine Aberrations in Alzheimer's Disease, Parkinson's Disease and Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis.

ABSTRACT: It has been suggested that cytokine-mediated inflammation plays a key role for the onset and/or development of neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD) and Amyotrophic lateral sclerosis (ALS). However, clinical studies have yielded inconsistent results for the aberrant cytokine levels in circulation of patients with AD, PD, and ALS. Previous studies have used meta-analysis to address the inconsistent data for blood cytokine levels in the patients with AD, PD, and ALS. Here, we performed a systemic review of cerebrospinal fluid inflammatory cytokine data in patients with AD, PD and ALS, and sought to quantitatively summarize the CSF inflammatory cytokine data with a meta-analytical technique. The systematic search from Pubmed and Web of Science identified 71 articles with 2629 patients and 2049 controls for the meta-analysis. Random-effects meta-analysis demonstrated that CSF TGF-?, MCP-1, and YKL-40 levels were significantly elevated in AD patients when compared with controls. In addition, patients with PD had heightened levels of TGF-?1, IL-6, and IL-1? in CSF. Furthermore, G-CSF, IL-2, IL-15, IL-17, MCP-1, MIP-1?, TNF-?, and VEGF levels were significantly increased in patients with ALS as compared with controls. Taken together, these results not only strengthen the clinical evidence that neurodegenerative diseases are accompanied by the increased inflammatory response, but also reveal the unique inflammatory response profile in the central nervous system of patients with AD, PD and ALS. Given the robust associations between some cytokines and neurodegenerative diseases found in this meta-analysis, CSF inflammatory cytokines may be used as biomarkers for these diseases in the future.

SUBMITTER: Chen X

PROVIDER: S-EPMC6156158 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Cerebrospinal Fluid Inflammatory Cytokine Aberrations in Alzheimer's Disease, Parkinson's Disease and Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis.

Chen Xi X Hu Yang Y Cao Zongze Z Liu Qingshan Q Cheng Yong Y

Frontiers in immunology 20180919

It has been suggested that cytokine-mediated inflammation plays a key role for the onset and/or development of neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD) and Amyotrophic lateral sclerosis (ALS). However, clinical studies have yielded inconsistent results for the aberrant cytokine levels in circulation of patients with AD, PD, and ALS. Previous studies have used meta-analysis to address the inconsistent data for blood cytokine levels in the patients wi ...[more]

PMID: 30283455

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Project description:The present study used comparative proteomic analysis of cerebrospinal fluid (CSF) in amyotrophic lateral sclerosis (ALS) patients in order to identify proteins that may act as diagnostic biomarkers and indicators of the pathogenesis of ALS. This analysis was performed using isobaric tags for relative and absolute quantitation (iTRAQ) technology, coupled with 2-dimensional liquid chromatography/mass spectrometry. Database for Annotation, Visualization and Integrated Discovery software was utilized for bioinformatic analysis of the data. Following this, western blotting was performed in order to examine the expression of 3 candidate proteins in ALS patients compared with healthy individuals [as a normal control (NC) group] or patients with other neurological disease (OND); these proteins were insulin-like growth factor II (IGF-2), glutamate receptor 4 (GRIA4) and leucine-rich α-2-glycoprotein 1 (LRG1). Clinical data, including gender, age, disease duration and ALS functional rating scale (ALSFRS-R) score, were also collected in the ALS patients. Multiple linear regression analysis was performed between the clinical data and the results of western blot analysis. A total of 248 distinct proteins were identified in the ALS and NC groups, amongst which a significant difference could be identified in 35 proteins; of these, 21 proteins were downregulated and 14 were upregulated. These differentially-expressed proteins were thus revealed to be associated with ALS. The western blot analysis confirmed a proportion of the data attained in the iTRAQ analysis, revealing the differential protein expression of IGF-2 and GRIA4 between the ALS and NC groups. IGF-2 was significantly downregulated in ALS patients (P=0.017) and GRIA4 was significantly upregulated (P=0.016). These results were subsequently validated in the 35-patient ALS and OND groups (P=0.002), but no significant difference was identified in LRG1 expression between these groups. GRIA4 protein expression was higher in male than female patients and was positively correlated with the ALSFRS-R score, meaning that GRIA4 expression was negatively correlated with the severity of ALS, while IGF-2 and LRG1 expression did not correlate with any clinical data. The present study thus demonstrated that GRIA4 expression levels, as a marker of severity, may be used as a reference for the timing of treatment, and that IGF-2 may serve as an effective biomarker of ALS progression.

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Dataset Information

Cerebrospinal Fluid Inflammatory Cytokine Aberrations in Alzheimer's Disease, Parkinson's Disease and Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis.

Publications

Cerebrospinal Fluid Inflammatory Cytokine Aberrations in Alzheimer's Disease, Parkinson's Disease and Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis.

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