2023 Alzheimer's Association Research Grant (AARG)
Alzheimer’s Disease Augments Cerebral Artery Apoptosis to Oxidative Stress
How might reactive molecules contribute to changes in brain blood flow seen in Alzheimer’s?
Charles Norton, Ph.D.
University of Missouri-Columbia
Columbia, MO - United States
Background
Blood vessels in the head and neck transport oxygen and nutrients that are critical for healthy brain function. During Alzheimer’s, impaired blood flow to the brain can negatively impact an individual’s memory and brain function.Several kinds of cells comprise blood vessels and help maintain healthy blood flow. These include endothelial cells, which line blood vessels, and smooth muscle cells, which help arteries (blood vessels) contract and relax. These cells are replaced regularly in healthy blood vessels, as older cells die through a process known as apoptosis and new cells grow in their place. Cells may undergo apoptosis early due to stressors in their environment including reactive oxygen species (ROS), reactive molecules that can build up and lead to cell damage.
Research Plan
Dr. Charles Norton and colleagues will study how cells that comprise blood vessels become more vulnerable to ROS during Alzheimer’s, and how this might contribute to problems with blood flow to the brain. To do this, Dr. Norton’s team will test the function of arteries collected from the brains of genetically engineered Alzheimer’s-like mice. The researchers will measure levels of ROS made in the arteries, and levels of cell death at various stages of disease. They will also expose the arteries to ROS and assess how this changes their function and ability to contract to determine how Alzheimer’s might influence the ability of blood vessels to recover from injury caused by ROS.
Next, the researchers will study small channels in the arteries that allow calcium to enter cells. Calcium is a key component of brain communication networks and an indicator of nerve cell health. Dr. Norton’s team will compare calcium flow through these channels in healthy mice and Alzheimer’s-like mice.
Impact
This study will deepen the understanding of how brain blood flow changes in Alzheimer’s and identify potential areas for therapeutic targets.