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2016 Grants - Liao
Is Dysfunctional eNOS a Major Contributing Factor for Sporadic Alzheimer’s?
Francesca-Fang Liao, Ph.D.
University of Tennessee Health Science Center
2016 Zenith Fellows Award
How is a protein that regulates blood flow involved in the development of Alzheimer’s-associated brain changes?
Most people who get Alzheimer’s disease are said to have “sporadic” Alzheimer’s meaning it is not known to be caused by a specific genetic variation. In many cases of sporadic Alzheimer’s, blood flow in the brain decreases long before clinical symptoms are evident. This decrease in blood flow may even predict that someone is at high risk of developing Alzheimer’s or other dementias in the future. Because of this link, scientists want to better understand the causes of decreased blood flow in the brain.
Blood flow in the brain and elsewhere is controlled by many factors, but one powerful factor is a protein known as eNOS (endothelial nitric oxide synthase). eNOS generates nitric oxide, which is a molecule that helps regulate blood flow in the brain. Recent studies have shown that low levels of eNOS in blood vessels may contribute to brain changes associated with Alzheimer’s disease.
Francesca-Fang Liao, Ph.D., and colleagues have proposed an extensive set of studies to characterize how loss of eNOS function affects brain blood vessels and may lead to brain damage in Alzheimer’s disease. The researchers will use mice genetically modified to have low levels of eNOS to study how this change affects blood flow and leads to the formation of small blood clots in the brain. They will also use advanced brain imaging to determine if low levels of eNOS affect the accumulation of amyloid plaques in the blood vessels, a condition known as cerebral amyloid angiopathy (CAA) that can lead to dementia. In addition, the research team will study brain tissue from people who had Alzheimer’s and CAA to determine how levels of eNOS relate to Alzheimer’s-associated brain changes.
The research conducted by Dr. Liao and colleagues will explore how alterations in a biochemical pathway can lead to abnormal changes in brain blood flow and may be involved in the early stages of Alzheimer’s disease. The results of these studies could lead to new ways to recognize people at risk and possibly identify novel targets for the development of drugs to prevent or slow disease progression.