Vascular inflammatory, oxidative and protease-based processes: implications for neuronal cell death in Alzheimer's disease.

A substantial literature demonstrates activation of inflammatory processes in the Alzheimer's disease (AD) brain and an association between inflammation and oxidative stress. We have shown that brain microvessels from AD patients express high levels of inflammatory proteins and that these proteins evoke release of the neurotoxic protease thrombin from brain endothelial cells. The objective of this study was to determine the effects of inflammatory proteins on brain endothelial cell reactive oxygen species generation, protease release and cell apoptosis.

Injured brain endothelial cells release neurotoxic thrombin.

The multifunctional serine protease thrombin has been shown to be neurotoxic in vitro and in vivo and is demonstrable in the Alzheimer disease (AD) brain. We have documented that in AD the cerebral microvasculature is a source of inflammatory and neurotoxic proteins. The objective of this study was to determine if injured brain endothelial cells could be a source of neurotoxic thrombin.

Oxidized LDLs affect nitric oxide and radical generation in brain endothelial cells.

There is an increase in the generation of reactive oxygen species and nitric oxide in the cerebral microcirculation in Alzheimer's disease. The factors that cause this increase in oxidative stress have not been identified. Increasing evidence suggests that there are common mechanisms in atherosclerosis and Alzheimer's disease.