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)-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.
Swardfager
Walter
W
Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.
Lanctôt
Krista
K
Rothenburg
Lana
L
Wong
Amy
A
Cappell
Jaclyn
J
Herrmann
Nathan
N
D000544:Alzheimer Disease / Q000097:blood* / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D016207:Cytokines / Q000097:blood* / Q000134:cerebrospinal fluid*; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood / Q000134:cerebrospinal fluid
D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators