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Decoding Ties Between Vascular Disease, Alzheimer’s

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Seeking a better understanding of vascular contributions to Alzheimer’s disease, the National Institutes of Health has launched the Molecular Mechanisms of the Vascular Etiology of Alzheimer’s Disease (M²OVE-AD) Consortium, a team-science venture to build a nuanced model of Alzheimer’s disease that more accurately reflects its many causes and pathways. Scientists have long been interested in how the vascular system — the body’s network of large and small blood vessels — may be involved in the onset and progression of Alzheimer’s disease and related dementias. Scientists from diverse fields using the latest methodologies will work collaboratively towards shared goals: to dissect the complex molecular mechanisms by which vascular risk factors influence Alzheimer’s disease and identify new targets for treatment and prevention.

Developed by the National Institute on Aging (NIA) and the National Institute of Neurological Disorders and Stroke (NINDS), both part of NIH, the five-year, $30-million program brings together over a dozen research teams working on five complementary projects. Harnessing the power of new molecular technologies and big data analytics, the teams will make biological datasets available to the wider research community.

“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,” said NIA Director Richard J. Hodes, M.D. “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.”

The teams will generate several layers of molecular data from brain tissue donated by deceased Alzheimer’s research participants and from blood cells and plasma donated by living study participants with various types of vascular risk. They will then develop mathematical models of the molecular processes that link vascular risk factors to Alzheimer’s onset and progression by combining molecular data with data on cognition, brain imaging and several measures of vascular health.

In parallel, the teams will use a number of animal models that show different vascular disease traits to tease out the molecular mechanisms linking vascular risk factors and Alzheimer’s and to test the predictions made from the analyses of the human data.

“A growing body of research suggests vascular damage often contributes to Alzheimer’s disease,” said Roderick Corriveau, Ph.D., program director, NINDS. “This focused collaborative effort may push our understanding of Alzheimer’s disease over a tipping point and facilitate the development of better treatments for those who are suffering.”

M²OVE-AD builds upon the open-science approach and the big-data infrastructure established by the Accelerating Medicines Partnership-Alzheimer’s Disease (AMP-AD), a precompetitive partnership between NIH, industry and nonprofit organizations to speed the discovery of promising therapeutic targets and disease biomarkers.

“Breaking down the traditional barriers to collaboration and data-sharing is key to moving the science forward, so we’ve ensured that the discoveries each team makes can be rapidly shared among the Consortium and the wider research community,” said Suzana Petanceska, Ph.D., senior advisor for strategic development and partnerships in the NIA Division of Neuroscience. “We’ve also established a panel of external leading experts to help shape the direction of M2OVE-AD research and potentially, bring about new partnerships and avenues of investigation.”