Correlation analysis of capillary APOE, VEGF and eNOS expression in Alzheimer brains.

Vasoactive regulatory and transport proteins can modify the transendothelial blood-brain barrier (BBB) transport of beta-amyloid. Dysfunction of one or more of these proteins is hypothesized to contribute to the pathogenesis of Alzheimer's disease (AD). In this study we investigated superior temporal and occipital cortical sections from ten AD and ten control group brains (CG). They were examined using immunohistochemical techniques staining for β(42) amyloid, APOE, VEGF and eNOS. The densities of senile plaques (SPs) and APOE, VEGF and eNOS positive capillaries in each region and in each AD and CG condition were compared using nonparametric statistical analysis. In the AD cases, there were significant negative correlations between APOE positive capillaries and β(42) amyloid SPs, and positive correlations between APOE positive capillaries and VEGF and eNOS positive capillaries. These results demonstrate the increased presence of APOE activity in AD brain capillaries, and that there is a positive correlation between the expression of APOE and each of VEGF and eNOS in the capillaries of AD brains. It is possible, therefore, that the down regulation of APOE in AD brains may contribute significantly to the pathogenesis of SP lesion development by modulating brain β-amyloid burden. The specific interrelationship between APOE, VEGF and eNOS activity at the BBB requires further investigation.