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)-alpha (3.25 [.76, 5.74] pg/mL, p = .01, N = 680/447, 14 studies), IL-1beta (.55 [.32, .78] pg/mL, p < .00001, N = 574/370, 10 studies), transforming growth factor (TGF)-beta (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-gamma, or C-reactive protein in AD subjects compared with control subjects. There were significantly higher concentrations of TGF-beta (7.81 [2.27, 13.35] pg/mL, p =.006, N = 113/114, 5 studies) but not IL-6, TNF-alpha, and IL-1beta 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-alpha, IL-1beta, TGF-beta, IL-12 and IL-18 and higher CSF concentrations of TGF-beta.
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