Decreased IL-8 levels in CSF and serum of AD patients and negative correlation of MMSE and IL-1β

Abstract

Background: It is widely accepted that neuroinflammatory processes play an important role in the pathogenesis of Alzheimer's disease (AD) and high levels of cytokines and chemokines are detected around Aβ plaques.

Methods: As neuroinflammation is involved in the development and progression of AD, we measured the pro-inflammatory cytokines interleukin 1β (IL-1β), IL-8 and tumor necrosis factor α (TNF-α) in serum and cerebrospinal fluid (CSF) samples from 45 AD patients and 53 age-matched control subjects using a highly sensitive multiplex electrochemiluminescence assay. To address the association with disease progression we correlated cognitive status with cytokine levels.

Results: CSF as well as serum IL-8 levels were found to be significantly lower in AD patients than in controls (p = 0.02). A statistically significant inverse correlation was observed between the CSF level of IL-1β and the MMSE score (r_s = -0.03, p = 0.02). We therefore stratified the AD patients by their MMSE scores into three equal groups and found that in the AD group with the most severe cognitive impairment CSF-IL-1β was significantly increased compared to age-matched controls (p < 0.05), whereas in the other investigated groups the increase was not statistically significant.

Conclusion: Our results confirm data suggesting that cytokine alterations are involved in AD pathogenesis and may be helpful as a biomarker for monitoring disease progression.

Keywords: Alzheimer’s disease; Cytokines; Neuroinflammation.

Fig. 1

Cytokine levels in CSF samples of AD patients compared to controls. Box plots comparing CSF IL-1β, IL-8 and TNF-α levels between AD patients and age-matched controls. a IL-1β levels were not altered in AD patients compared to controls (p = 0.12). b IL-8 levels, by comparison, were significantly reduced in AD patients (p = 0.02). c TNF-α showed no significant difference (p = 0.83). Dark horizontal lines represent the mean, with the box representing the 25^th and 75^th percentiles of the observed data, the whiskers representing the 5^th and 95^th percentiles, and outliers represented by dots. P values were calculated using the Mann-Whitney Rank sum test

Fig. 2

Cytokine levels in serum of AD patients and age-matched controls. Box plots comparing Serum IL-1β, IL-8 and TNF-α levels between AD patients and age-matched controls. a IL-1β levels were unchanged (p = 0.81). b IL-8 levels were significantly reduced in AD patients (p = 0.02). c TNF-α showed a slight reduction in AD patients but the observed effect was not significant (p = 0.05). Dark horizontal lines represent the mean, with the box representing the 25^th and 75^th percentiles of the observed data, the whiskers representing the 5^th and 95^th percentiles, and outliers represented by dots. P values were calculated using the Mann-Whitney Rank sum test

Fig. 3

Analysis of IL-1β levels in CSF of stratified patients by MMSE. CSF IL-1β levels inversely correlated with MMSE score. To further analyze this correlation, AD patients were grouped according to their MMSE score and IL-1β levels were compared to age-matched controls. Box plots represent median levels of CSF IL-1β with the box representing the 25^th and 75^th percentiles of the observed data, the whiskers showing the 5^th and 95^th percentiles and dots representing outliers. The MMSE (11-18) group IL-1β was significantly increased compared to the other investigated groups (p < 0.05, ANOVA on Ranks, Dunn’s method)