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Center for Genetics & Genomics of Alzheimer’s Disease Established

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A five-year, projected $10.8 million award from the National Institute on Aging (NIA), part of the National Institutes of Health (NIH), will establish the Coordinating Center for Genetics and Genomics of Alzheimer’s Disease, a joint venture of researchers from the Perelman School of Medicine at the University of Pennsylvania and five other institutions. Penn will receive an estimated $4.5 million from the grant.

The Center is led by Gerard D. Schellenberg, PhD, a professor of Pathology and Laboratory Medicine and Li-San Wang, PhD, an associate professor of Pathology and Laboratory Medicine, in partnership with investigators from five other sites  -- Boston University, Case Western Reserve University, Columbia University, the University of Miami, and the University of Indiana.

“By coordinating the identification of Alzheimer’s-related genes, the Center’s team aims to find new therapeutic targets to reduce the economic and human burden caused by this disease,” Schellenberg said. “This is an exciting opportunity to apply new technologies to improve our understanding of the biological pathways underlying this devastating disease. The new center will stimulate collaborations between hundreds of U.S. and international Alzheimer’s genetics researchers by aggregating and analyzing very large data sets and sharing the results. This type of global interaction is needed if we are to make progress in solving this devastating illness.”

Alzheimer’s disease, a progressive neurodegenerative disorder, has become an epidemic that currently affects as many as five million people age 65 and older in the United States, with economic costs that are comparable to, if not greater than, caring for those of heart disease or cancer. Available drugs only marginally affect disease severity and progression. While there is no way to prevent this disease, the discovery of genetic risk factors for Alzheimer’s is bringing researchers closer to learning how the genes work together and may help identify the most effective interventions.

“The Genomics Center will be a state-of-the-art national clearinghouse for Alzheimer’s genomics information based at Penn,” Wang said. “We have an important mission to move the field of Alzheimer’s genetics forward by coordinating all NIA-funded activities for the Alzheimer’s Disease Sequencing Project.”

Center collaborators will collect and “harmonize” available AD genetics and associated physiological data into a common database to maximize statistical power to find therapeutic targets.

“Data-sharing and collaboration among cutting-edge research teams is key to advancing our understanding of complex genetic underpinnings of Alzheimer’s and related dementias,” said NIA director Richard Hodes, MD. “This new Center will play an important role in achieving our nation’s ultimate research goal, outlined under the National Plan to Address Alzheimer’s Disease to prevent and effectively treat Alzheimer’s disease by 2025.”

The Genomics Center will also bring in data from other non-NIA-funded studies, reprocess into a consistent format, and add to the common database housed at the NIA Genetics of Alzheimer’s Disease Data Storage Site (NIAGADS), the national genetics data repository for Alzheimer’s disease developed and maintained by Wang’s team since 2012 and the Data Coordinating Center for the ADSP. The Genomic Center will amass genomic sequence data from subjects with Alzheimer’s disease and elderly cognitively normal subjects and use these data to identify genes that cause or protect against AD and other diseases.

“As the amount of data acquired increases, this will be a valuable resource for the study of other genetic disorders at Penn and other institutions,” Wang said.

The NIH Alzheimer’s Disease Sequencing Program (ADSP), a collaboration that also began in 2012 between NIA and the National Human Genome Research Institute (NHGRI), also part of NIH, has been analyzing data from 6,000 volunteers with Alzheimer’s disease and 5,000 older cognitively normal, unaffected individuals. In addition, the teams will study genomic data from 111 large families with multiple Alzheimer’s disease members, of Caucasian and Caribbean Hispanic descent to identify rare genetic variants.  For the next phase of the project, the new Center will analyze new sequence data from an additional 3,000 AD cases.

In 2014, Schellenberg and Wang were also awarded NIA funds for the Consortium for Alzheimer’s Sequence Analysis (CASA) to facilitate the analyses of the first stage of ADSP and additional non-ADSP sequence data to detect protective and risk gene variants for AD. CASA is a collaboration of Penn and Jonathan Haines, PhD at Case Western Reserve University; Richard Mayeux, MD, at Columbia University; Margaret Pericak-Vance, PhD, at the University of Miami; and Lindsay Farrer, PhD, at Boston University.