Increased plasma levels of interleukin-1, interleukin-6 and α-1-antichymotrypsin in patients with Alzheimer's disease: peripheral inflammation or signals from the brain?

Abstract

Plasma concentrations of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), C reactive protein (CRP) and alpha-1-antichymotrypsin (ACT) in 145 patients with probable Alzheimer's disease (AD) and 51 non-demented controls were measured. To investigate the cellular activation of peripheral immune system, plasma levels of neopterin were also investigated. Plasma levels of IL-1 were detectable in 17 patients with AD (13%) and only in one control (2%) and average levels of IL-1 were higher in AD patients than in controls (p < 0.001). IL-6 plasma levels were detectable in a higher proportion of AD and controls (53% and 27%, respectively), and were increased in patients with AD (p < 0.001). Plasma levels of ACT were increased in patients with AD (p < 0.001) and CRP levels were in the normal range. Plasma levels of neopterin were slightly lower in AD patients than in controls, but differences were not statistically significant. No significant correlation was observed between IL-1 and IL-6 levels or neopterin and cytokine levels in plasma from AD patients. Plasma levels of ACT negatively correlated with cognitive performances, as assessed by the mini mental state examination (MMSE; R = -0.26, p < 0.02) and positively correlated with the global deterioration state (GDS) of AD patients (R = 0.30, p < 0.007). Present findings suggested that detectable levels of circulating cytokines and increased ACT might not be derived by activation of peripheral immune system of AD patients. Detection of these molecules might be used for monitoring the progression of brain inflammation associated with AD.

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“…14 Data supporting the idea that peripheral IL-6 levels represent those in brain is lacking, but evidence suggests that IL-6 does cross the blood brain barrier and peripheral levels may represent spillover from the central nervous system and be a marker of inflammation. 15,16 Interleukin 6 may also affect cognition through an interaction with vascular disease as there is evidence that it increases the risk of diabetes mellitus and cardiovascular events. 17, 18 In addition, the finding that IL-6 and CRP levels above the median have predicted cognitive decline in those with, but not without, the metabolic syndrome implicates a vascular mechanism.…”

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