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A meta-analysis of cytokines in Alzheimer's disease.

Abstract

BACKGROUND

Studies suggest that inflammation is involved in the neurodegenerative cascade leading to Alzheimer's disease (AD) pathology and symptoms. This study sought to quantitatively summarize the clinical cytokine data.

METHODS

Original English language peer-reviewed studies measuring cytokine concentrations in AD and healthy control subjects were included. Mean (± standard deviation) cytokine concentrations for AD and control subjects were extracted.

RESULTS

Forty studies measuring peripheral blood cytokine concentrations and 14 measuring cerebrospinal fluid (CSF) cytokine concentrations were included. In peripheral blood, there were significantly higher concentrations (weighted mean difference [95% confidence interval]) of interleukin (IL)-6 (2.86 [1.68, 4.04] pg/mL, p < .00001, N[AD/control subjects] = 985/680, 14 studies), tumor necrosis factor (TNF)-α (3.25 [.76, 5.74] pg/mL, p = .01, N = 680/447, 14 studies), IL-1β (.55 [.32, .78] pg/mL, p < .00001, N = 574/370, 10 studies), transforming growth factor (TGF)-β (67.23 [28.62, 105.83] pg/mL, p = .0006, N = 190/158, 5 studies), IL-12 (7.60 [5.58, 9.62] pg/mL, p < .00001, N = 148/106, 5 studies), and IL-18 (15.82 [1.98, 29.66] pg/mL, p = .03, N = 131/94, 4 studies) but not of IL-4, IL-8, IL-10, interferon-γ, or C-reactive protein in AD subjects compared with control subjects. There were significantly higher concentrations of TGF-β (7.81 [2.27, 13.35] pg/mL, p =.006, N = 113/114, 5 studies) but not IL-6, TNF-α, and IL-1β in the CSF of AD subjects compared with control subjects.

CONCLUSIONS

These results strengthen the clinical evidence that AD is accompanied by an inflammatory response, particularly higher peripheral concentrations of IL-6, TNF-α, IL-1β, TGF-β, IL-12 and IL-18 and higher CSF concentrations of TGF-β.

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  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.

    , , , ,

    Source

    Biological psychiatry 68:10 2010 Nov 15 pg 930-41

    MeSH

    Alzheimer Disease
    Biomarkers
    Cytokines
    Humans
    Inflammation Mediators

    Pub Type(s)

    Journal Article
    Meta-Analysis
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    20692646

    Citation

    Swardfager, Walter, et al. "A Meta-analysis of Cytokines in Alzheimer's Disease." Biological Psychiatry, vol. 68, no. 10, 2010, pp. 930-41.
    Swardfager W, Lanctôt K, Rothenburg L, et al. A meta-analysis of cytokines in Alzheimer's disease. Biol Psychiatry. 2010;68(10):930-41.
    Swardfager, W., Lanctôt, K., Rothenburg, L., Wong, A., Cappell, J., & Herrmann, N. (2010). A meta-analysis of cytokines in Alzheimer's disease. Biological Psychiatry, 68(10), pp. 930-41. doi:10.1016/j.biopsych.2010.06.012.
    Swardfager W, et al. A Meta-analysis of Cytokines in Alzheimer's Disease. Biol Psychiatry. 2010 Nov 15;68(10):930-41. PubMed PMID: 20692646.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - A meta-analysis of cytokines in Alzheimer's disease. AU - Swardfager,Walter, AU - Lanctôt,Krista, AU - Rothenburg,Lana, AU - Wong,Amy, AU - Cappell,Jaclyn, AU - Herrmann,Nathan, Y1 - 2010/08/08/ PY - 2010/04/06/received PY - 2010/06/03/revised PY - 2010/06/08/accepted PY - 2010/8/10/entrez PY - 2010/8/10/pubmed PY - 2011/3/2/medline SP - 930 EP - 41 JF - Biological psychiatry JO - Biol. Psychiatry VL - 68 IS - 10 N2 - BACKGROUND: Studies suggest that inflammation is involved in the neurodegenerative cascade leading to Alzheimer's disease (AD) pathology and symptoms. This study sought to quantitatively summarize the clinical cytokine data. METHODS: Original English language peer-reviewed studies measuring cytokine concentrations in AD and healthy control subjects were included. Mean (± standard deviation) cytokine concentrations for AD and control subjects were extracted. RESULTS: Forty studies measuring peripheral blood cytokine concentrations and 14 measuring cerebrospinal fluid (CSF) cytokine concentrations were included. In peripheral blood, there were significantly higher concentrations (weighted mean difference [95% confidence interval]) of interleukin (IL)-6 (2.86 [1.68, 4.04] pg/mL, p < .00001, N[AD/control subjects] = 985/680, 14 studies), tumor necrosis factor (TNF)-α (3.25 [.76, 5.74] pg/mL, p = .01, N = 680/447, 14 studies), IL-1β (.55 [.32, .78] pg/mL, p < .00001, N = 574/370, 10 studies), transforming growth factor (TGF)-β (67.23 [28.62, 105.83] pg/mL, p = .0006, N = 190/158, 5 studies), IL-12 (7.60 [5.58, 9.62] pg/mL, p < .00001, N = 148/106, 5 studies), and IL-18 (15.82 [1.98, 29.66] pg/mL, p = .03, N = 131/94, 4 studies) but not of IL-4, IL-8, IL-10, interferon-γ, or C-reactive protein in AD subjects compared with control subjects. There were significantly higher concentrations of TGF-β (7.81 [2.27, 13.35] pg/mL, p =.006, N = 113/114, 5 studies) but not IL-6, TNF-α, and IL-1β in the CSF of AD subjects compared with control subjects. CONCLUSIONS: These results strengthen the clinical evidence that AD is accompanied by an inflammatory response, particularly higher peripheral concentrations of IL-6, TNF-α, IL-1β, TGF-β, IL-12 and IL-18 and higher CSF concentrations of TGF-β. SN - 1873-2402 UR - https://www.unboundmedicine.com/medline/citation/20692646/A_meta_analysis_of_cytokines_in_Alzheimer's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-3223(10)00601-3 DB - PRIME DP - Unbound Medicine ER -