Blood levels of cytokines highlight the role of inflammation in Alzheimer's disease

Abstract

Inflammation and angiogenesis have been defined as potential mechanisms associated with clinical progression from a cognitively normal state to Alzheimer's disease (AD). In this observational case-control study, we aimed to determine plasma levels of cytokines as indicators of inflammation involved in cognitive decline. We measured 30 plasma proteins in 49 controls (CTL), 36 individuals with mild cognitive impairment (MCI) and 52 patients diagnosed with probable AD. After applying strict filters for quantification limits, only 13 analytes were included in the analysis. Kruskal-Wallis tests showed significant differences between diagnostic groups for nine cytokines (IL-16, IL-7, VEGF, IL-8, eotaxin, MCP-1, MCP-4, MDC and TARC). Non-parametric MANCOVA showed that sex and diagnosis affected cytokine levels in the blood. To determine the sensitivity and specificity of the markers, we performed receiver operating characteristic (ROC) curve analysis. Only those analytes that showed an area under the curve (AUC) ≥ 0.70 were included in the multivariate logistic regression models to better understand the contribution of cytokines to clinical status. Three models: 1) CTL vs. AD; 2) CTL vs. MCI, and 3) MCI vs. AD were developed, with sex and age as covariates. In each model, two cytokines remained significantly different (model 1: IL-16 and MDC; model 2: eotaxin and MDC and model 3: IL-7 and VEGF). Taken together, this report identifies a set of plasma markers of inflammation and strengthens the role of glial biology in different clinical stages of AD.

Keywords: Chemoattractants; Dementia; Glial cells; Inflammation; Interleukins; Plasma.

Graphical abstract

Fig. 1

Cytokine plasma concentration levels between clinical categories. Only the nine cytokines whose concentration levels were significantly different between clinical categories are displayed. Violin plots show the frequency distribution of the data with individual data points superimposed. Dotted lines indicate the median and quartiles Q1 and Q3. ∗p < 0.05; ∗∗p < 0.01; ∗∗∗p < 0.001 (see Table S2 for detailed statistics and exact p-values). Abbreviations: CTL, cognitively normal subjects; MCI, mild cognitive impairment; AD, Alzheimer's disease.