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Emory team awarded $5.2 million to study vascular-Alzheimer's link

A team of Emory researchers was awarded a $5.2 million, five-year grant from the National Institute on Aging, part of the National Institutes of Health, to examine the connections between blood pressure regulation and Alzheimer’s disease. 

The lead investigators are Ihab Hajjar, MD, associate professor of neurology and medicine at Emory University School of Medicine and the Emory Alzheimer’s Disease Research Center, and Arshed Quyyumi, MD, professor of medicine and co-director of the Emory Clinical Cardiovascular Research Institute.

“It has been thought for many years that vascular disease and circulatory function contribute to the development of Alzheimer's disease, but the way this happens is unknown,” Hajjar says. “This initiative will uncover these mechanisms on a molecular and clinical level, so that new drugs can be designed and targeted to the right groups of patients."

The study builds on research suggesting that common blood pressure medications may reduce the risk that people with early signs of memory problems will develop Alzheimer’s. Scientists think that the molecules that drive Alzheimer’s disease and vascular disease are intertwined. For example, the most important genetic risk factor for Alzheimer’s, ApoE4, encodes a variant of a protein involved in transport of cholesterol.

The Emory study focuses on the roles of the renin-angiotensin system, the targets of common blood pressure medications, and endothelial cells, which line blood vessels, in the onset and progression of Alzheimer’s.

The Emory team will examine the molecular and vascular traits of 200 participants older than 50, with either normal cognition or mild cognitive impairment and early biological signs of Alzheimer’s. Over a two year period, participants will have evaluations to assess memory and cognition, brain scans, vascular ultrasounds, spinal taps, blood tests and blood pressure readings. 

Molecular data (genomic, epigenetic and metabolomic) will be combined with clinical information and used to build a network model of the interaction between vascular dysfunction and various Alzheimer's traits. A recently developed rat model of Alzheimer's will also be used to explore molecular details and the impact of blood pressure regulation.

The Emory study is part of a consortium, called Molecular Mechanisms of the Vascular Etiology of Alzheimer’s Disease (M²OVE-AD), coordinated by the National Institute on Aging and the National Institute of Neurological Disorders and Stroke. The five-year, $30 million M²OVE-AD program brings together over a dozen research teams working on five complementary projects.

"Despite evidence that the brains of most Alzheimer's patients have a variety of vascular lesions, and that mid-life diabetes and high blood pressure are major risk factors for Alzheimer's, our understanding of the molecular mechanisms involved is quite limited," says National Institute on Aging director Richard J. Hodes, MD. "M²OVE-AD will not only advance our understanding of these mechanisms, but also identify the molecular signatures—sets of genes, proteins and metabolites—that may be used as markers for disease risk or to track the effectiveness of promising therapies."

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