A Meta-Analysis of Cytokines in Alzheimer's Disease

• Published in: Biological psychiatry (1969) Vol. 68; no. 10; pp. 930 - 941
• Main Authors: Swardfager, Walter, Lanctôt, Krista, Rothenburg, Lana, Wong, Amy, Cappell, Jaclyn, Herrmann, Nathan
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 15.11.2010; Elsevier
• Subjects: Adult and adolescent clinical studies; Alzheimer Disease - blood; Alzheimer Disease - cerebrospinal fluid; Alzheimer's disease; Biological and medical sciences; Biomarkers - blood; Biomarkers - cerebrospinal fluid; clinical; cytokines; Cytokines - blood; Cytokines - cerebrospinal fluid; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Humans; inflammation; Inflammation Mediators - blood; Inflammation Mediators - cerebrospinal fluid; interleukin; Medical sciences; meta-analysis; Neurology; Organic mental disorders. Neuropsychology; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; meta-analysis; clinical; cytokines; interleukin; inflammation; Alzheimer's disease; Nervous system diseases; Alzheimer disease; Interleukin; Cytokine; Inflammation; Review; Cerebral disorder; Metaanalysis; Central nervous system disease; Degenerative disease
• ISSN: 0006-3223; 1873-2402; 1873-2402
• DOI: 10.1016/j.biopsych.2010.06.012

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. 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. 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. 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.