2024 Alzheimer's Association Research Grant to Promote Diversity (AARG-D)
Impact of arterial stiffening on cerebrovascular and cognitive function
How does blood vessel stiffening harm brain function?
Monica Santisteban, Ph.D.
Vanderbilt University
Nashville, TN - United States
Background
Blood vessels in the head and neck provide the brain with vital, oxygen-rich blood that is critical for brain cells’ ability to function properly. Inadequate blood flow can damage and eventually damage cells anywhere in the body, but the brain is especially vulnerable. In the brain, impaired blood flow can negatively impact a person’s memory and function.
Studies have shown that with aging, there is reduced blood flow to the brain and this may increase the risk for developing Alzheimer’s or another dementia. In addition, as individuals age they also develop a stiffening of their blood vessels, known as arteries. The stiffness of arteries can affect the heart’s ability to pump blood throughout the body and may change the pressure at which blood flows to the brain. Further, Studies have shown that increased stiffness in arteries is associated with cognitive deficits. However, it is not well-known what drives stiffening of arteries and how it can harm brain function.
In preliminary studies, Dr. Monica Santestiban found that high blood pressure caused by arterial stiffening led to inflammation in mice, which preceded cognitive impairment. Mice with reduced inflammation were protected against cognitive decline.
Research Plan
Dr. Santestiban and colleagues will study whether arterial stiffening leads to inflammation and cognitive deficits. They will use two groups of mice, one that is given a drug to increase arterial stiffening and blood pressure for two weeks and another that is not given treatment. They will then assess cognition, blood vessel function, and levels of inflammation in the brain and body in both groups of mice.
Additionally, to determine the impact of arterial stiffening and inflammation as it relates to Alzheimer’s, they will repeat these experiments on genetically-engineered Alzheimer’s-like mice—some that are given the drug to increase arterial stiffening and blood pressure for two weeks, and some that are given no treatment. In addition to measuring cognition, blood vessel function, and inflammation in these mice, they will also measure markers of Alzheimer’s.
Impact
The results of this project may elucidate how factors related to blood flow contribute to Alzheimer’s symptoms. Understanding how blood vessel problems can damage the brain is important for developing new ways to protect it.