Abstract TMP111: Phenotypic Alterations of Brain Microvascular Endothelium in a Murine Model of Alzheimer Disease

Abstract

Background: Alzheimer disease (AD) is characterized by progressive neuronal disorder that cause dementia, and is recognized as a major cause of death in the elderly population. Recent our in vitro findings suggest the possibilities that autophagy-associated endothelial dysfunction might be involved in the pathogenesis of AD. Methods: Electron microscopy (EM) and immunohistological analysis were performed on brain tissues of APP23, a mouse model of AD, and age-matched wild type mice. Results: The Morris water maze test showed cognitive disturbance in 8-month old APP23 mice but not in wild type mice. Notably, EM revealed that the densities of hippocampal capillary were significantly lower in APP23 mice as compared to those in wild type mice. The reduction in hippocampal microvessels was more apparent in 24-month old APP23 mice. Immunostaining with antibodies against ß-amyloid (Aß) and alpha-smooth-muscle-actin showed that Aß deposition was not limited to neural cells but to microvessels in hippocampus and cortex. Importantly, EM analysis revealed autophagy induction in hippocampal capillary endothelium in 8-month old APP23 mice. In addition, the number of microvessels with autophagic endothelium was significantly increased in 24-month-old APP23 mice. Furthermore, the advanced stages of autophagy fused with lysosome were detected in both neurovascular endothelium and neural cells. Conclusions: The present study indicate that phenotypic alteration of neurovascular endothelium might be the earlier pathological events in brain with AD, suggesting important implications for therapeutic approaches of AD.