Abstract
Inflammatory mediators are highly expressed in the Alzheimer's disease (AD) brain. We have shown that in AD the cerebral microcirculation is a rich source of cytokines and chemokines including interleukins (IL) 1β, IL-6, IL-8, tumor necrosis factor-α, and monocyte chemoattractant protein-1. However, the factors that regulate expression of these inflammatory proteins have not been defined. The objective of this study is to compare expression of macrophage inflammatory protein 1-α (MIP-1α) in brain microvessels isolated from AD patients to vessels from age-matched controls and further to determine whether expression of MIP-1α in brain endothelial cells is altered by oxidative stress. The data show that brain AD-derived microvessels express high levels of MIP-1α mRNA and release high levels of MIP-1α protein compared to brain microvessels isolated from controls. Treatment of brain endothelial cell cultures with menadione, a superoxide releasing compound, hydrogen peroxide, lipopolysacharride, or oxidatively modified low density lipoproteins (LDL) (Ox-LDL, HNE-LDL) results in a dose- dependent increase in MIP-1α mRNA levels and MIP-1α release into the media. These results suggest that oxidative and lipid insults to the brain microvasculature are likely to contribute to the inflammatory milieu of the AD brain.