A Meta-Analysis of Cytokines in Alzheimer's Disease

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 1 beta (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 1 beta 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 1 beta TGF beta IL 12 and IL 18 and higher CSF concentrations of TGF beta