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      IL-1β, IL-6, TNF- α and CRP in Elderly Patients with Depression or Alzheimer’s disease: Systematic Review and Meta-Analysis

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          Abstract

          We carried out systematic review and meta-analysis to evaluate whether peripheral levels of pro-inflammatory markers including Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF- α) and C-Reactive Protein (CRP) are significantly higher in elderly with depression and Alzheimer’s disease. We searched Pubmed, PsycINFO and Embase, and thirty-four relevant studies (2609 with Depression, 1645 with Alzheimer’s disease and 14363 Controls) were included. Compared with controls, IL-1β (pooled standardized mean difference [SMD]: 0.642; 95% confidence interval [CI]: 0.078–1.206; significant heterogeneity: I 2 = 86.28%) and IL-6 (pooled SMD: 0.377; 95% CI: 0.156–0.598; significant heterogeneity: I 2 = 88.75%) were significantly elevated in depression. There was no difference in TNF-α (p = 0.351) and CRP (p = 0.05) between those with depression and controls. Compared with controls, IL-1β (pooled SMD: 1.37, 95% CI: 0.06–2.68, significant heterogeneity: I 2 = 96.01%) was significantly elevated in Alzheimer’s disease. There were no differences in IL-6 (p = 0.138), TNF-α (p = 0.451) and CRP (p = 0.07) between elderly with Alzheimer’s disease and controls. After Bonferroni adjustment, only IL-6 remained significantly higher in depression. Elderly with depression have higher IL-6 than controls, while those with Alzheimer’s disease did not have higher peripheral inflammatory markers.

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          Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.

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            Gene regulation and DNA damage in the ageing human brain.

            The ageing of the human brain is a cause of cognitive decline in the elderly and the major risk factor for Alzheimer's disease. The time in life when brain ageing begins is undefined. Here we show that transcriptional profiling of the human frontal cortex from individuals ranging from 26 to 106 years of age defines a set of genes with reduced expression after age 40. These genes play central roles in synaptic plasticity, vesicular transport and mitochondrial function. This is followed by induction of stress response, antioxidant and DNA repair genes. DNA damage is markedly increased in the promoters of genes with reduced expression in the aged cortex. Moreover, these gene promoters are selectively damaged by oxidative stress in cultured human neurons, and show reduced base-excision DNA repair. Thus, DNA damage may reduce the expression of selectively vulnerable genes involved in learning, memory and neuronal survival, initiating a programme of brain ageing that starts early in adult life.
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              Interleukin (IL)-6, tumour necrosis factor alpha (TNF-α) and soluble interleukin-2 receptors (sIL-2R) are elevated in patients with major depressive disorder: a meta-analysis and meta-regression.

              Many studies have explored the association between soluble interleukin-2 receptor (sIL-2R), cytokines and major depressive disorder (MDD). However, the results of these studies were not consistent. The aim of our study is to compare the levels of sIL-2R and cytokines in the blood between MDD patients and controls by a meta-analysis and to identify moderators accounting for potential heterogeneity in the levels of sIL-2R and cytokines in MDD patients versus controls by meta-regression analyses. A comprehensive literature search was performed to identify studies comparing the levels of sIL-2R and cytokines between MDD patients and controls. We pooled the effect sizes for standardized mean differences (SMD) of the levels of sIL-2R and cytokines. We also performed meta-regression and sensitivity analyses to investigate the roles of age, gender, sample type, ethnic origin and selected studies' quality in explaining potential heterogeneity and differences in results respectively. Twenty-nine studies were selected for this analysis. The levels of sIL-2R, TNF-α and IL-6 in MDD patients were significantly higher than those of healthy controls (SMD=0.555, p<0.001, SMD=0.567, p=0.010; SMD=0.680, p<0.001). Mean age of all subjects was a significant moderator to explain the high heterogeneity of IL-6. Sensitivity analysis found that European but not non-European subjects have higher levels difference of sIL-2R, TNF-α and IL-1β between MDD patients and controls. The severity of MDD was not considered. The blood levels of sIL-2R, TNF-α and IL-6 were significantly higher in MDD patients than controls. Age, samples source and ethnic origins may play a potential role in heterogeneity. Copyright © 2011 Elsevier B.V. All rights reserved.
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                Author and article information

                Contributors
                Su_hui_ho@nuhs.edu.sg
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                13 August 2018
                13 August 2018
                2018
                : 8
                : 12050
                Affiliations
                [1 ]ISNI 0000 0004 0451 6143, GRID grid.410759.e, Department of Internal Medicine, , National University Health System, ; Singapore, Singapore
                [2 ]ISNI 0000 0001 2180 6431, GRID grid.4280.e, Alice Centre for Nursing Studies, Yong Loo Lin School of Medicine, , National University of Singapore, ; Singapore, Singapore
                [3 ]ISNI 0000 0001 2180 6431, GRID grid.4280.e, Biomedical Institute for Global Health Research and Technology, , National University of Singapore, ; Singapore, Singapore
                [4 ]ISNI 0000 0004 0451 6143, GRID grid.410759.e, Department of Psychological Medicine, , National University Health System, ; Singapore, Singapore
                [5 ]ISNI 0000 0001 2157 2938, GRID grid.17063.33, Institute of Medical Science, , University of Toronto, ; Toronto, ON Canada
                [6 ]ISNI 0000 0004 0474 0428, GRID grid.231844.8, Mood Disorders Psychopharmacology Unit, , University Health Network, ; Toronto, ON Canada
                [7 ]ISNI 0000 0001 2157 2938, GRID grid.17063.33, Department of Psychiatry, , University of Toronto, ; Toronto, ON Canada
                [8 ]ISNI 0000 0001 2157 2938, GRID grid.17063.33, Department of Toxicology and Pharmacology, , University of Toronto, ; Toronto, ON Canada
                Article
                30487
                10.1038/s41598-018-30487-6
                6089986
                30104698
                27d16d71-caa4-4c2a-ac14-5053b72b1eb1
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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                : 30 August 2017
                : 1 August 2018
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