Plasma neopterin level as a marker of peripheral immune activation in amnestic mild cognitive impairment and Alzheimer's disease

Abstract

Alterations of the immune system play important roles in Alzheimer's disease (AD). The primary purpose of this study was to compare the plasma levels of neopterin, a marker of cellular immune activity, in amnestic mild cognitive impairment (aMCI), early (mild to moderate) AD, and cognitively normal controls. In addition, the correlation of plasma neopterin with interferon-gamma (IFN-γ) and interleukin-6 (IL-6) was also examined. Plasma samples from patients with mild-to-moderate AD (N = 34), aMCI (N = 27), and cognitively normal controls (N = 30) were obtained from the Johns Hopkins Alzheimer's Disease Research Center. Plasma neopterin, IFN-γ, and IL-6 levels were measured using commercially available ELISAs. Multiple linear regression was performed to study differences in the baseline neopterin levels between normal, aMCI, and AD patients. Pearson correlation coefficients were estimated for neopterin and IFN-γ and IL-6 levels. All analyses were conducted using SAS (SAS Institute, Inc., Cary, NC) and GraphPad Prism version 5.00 for Window (GraphPad Software, San Diego, CA, USA). AD subjects had significantly higher neopterin values compared with aMCI (β = 0.202, p = 0.004) and normal (β = 0.263, p = 0.0004) subjects. There was no statistically significant difference between normal and aMCI subjects. Significant associations between neopterin and IFN-γ (r = 0.41, p < 0.0001) and IL-6 (r = 0.35, p = 0.0006) levels were found. Our study demonstrates that peripheral immune response may be stronger in later stages of AD pathophysiology, when dementia has developed.