Grant: Project Grant

The human brain requires adequate blood flow to perform its many functions. A complex network of arteries, capillaries and veins called the cerebrovasculature direct important nutrients throughout the brain. In structure, this network can be described as resembling the many branches in a tree. Alzheimer's disease (AD) is a debilitating brain disorder and the most common form of dementia in the elderly. An estimated 60-90 % of AD patients have cerebrovasculature abnormalities; this means that their brains fail to receive all the necessary nutrients from the blood. Individuals with diabetes and hypertension have an even higher risk of developing AD. It is thought that these diseases directly damage the cerebrovasculature. Unfortunately, we still do not understand why the cerebrovasculature fails to do its job in AD. Capillaries are the smallest blood vessels and they are surrounded by endothelial cells. Together with other cells called pericytes and astrocyte endfeet, brain capillary endothelial cells form the blood-brain-barrier. This barrier is vital: It oversees the exchanges between the brain and blood, and controls brain vascular functions. CD2AP is a protein that we have found to be highly enriched in the cerebrovasculature, particularly in brain capillary endothelial cells. Genetic studies show that abnormalities in this protein contribute to AD. Levels of CD2AP are also altered in patients who died with AD. Our research studies will investigate the roles of CD2AP in brain capillary endothelial cells, as well as its contribution to the blood-brain-barrier and how it functions. We intend to shed new light on the causes of AD, particularly on the associated vascular defects. This new health knowledge will serve to develop treatment of the impaired cerebrovasculature in AD patients.