Elsevier

Biological Psychiatry

Volume 68, Issue 10, 15 November 2010, Pages 930-941
Biological Psychiatry

Archival Report
A Meta-Analysis of Cytokines in Alzheimer's Disease

https://doi.org/10.1016/j.biopsych.2010.06.012Get rights and content

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.

Section snippets

Data Sources

All analyses were performed according to PRISMA guidelines (22). While PRISMA guidelines have focused on randomized trials, the PRISMA statement specifies “PRISMA can also be used as a basis for reporting systematic reviews of other types of research.” English language literature was searched using Medical Literature Analysis and Retrieval System Online (National Library of Medicine, Bethesda, Maryland), Excerpta Medica Database (Elsevier, Amsterdam, The Netherlands), PsycINFO (American

Literature Search Findings

Search criteria returned 206 unique records of cytokine studies in living subjects with AD (Figure S1 in Supplement 1) and 10 records published in languages other than English. Of the English language records, 98 were excluded based on the publication type being a review rather than a clinical study and 22 were excluded based on reporting only cytokine excretion from peripheral blood following exogenous stimulation. Thus, 86 studies were identified for review.

A total of 73 cross-sectional

Discussion

This meta-analysis reports significantly higher concentrations of the proinflammatory cytokines IL-6, TNF-α, IL-1β, IL-12, and IL-18 in the peripheral blood of AD subjects compared with control subjects. Evidence was particularly strong for IL-6, IL-12, and IL-18, which were significantly associated with AD in subgroups of studies that matched control subjects for age, in which subjects were free of inflammatory comorbidity and that used comparable assay techniques. While both positive and

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