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University of Miami researchers awarded 2 NIH contracts to study Alzheimer’s

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Alzheimer's disease is the leading cause of dementia in the elderly and occurs in all ethnic and racial groups. It affects more than 5 million people age 65 and older in the United States alone and there is currently no effective treatment or cure. By identifying the genetic factors that contribute to Alzheimer's disease risk or protect against it, researchers hope to improve diagnosis, treatments and potentially prevent the disease.

Researchers from the University of Miami Miller School of Medicine's John P. Hussman Institute for Human Genomics (HIHG) have been awarded two new contracts from the National Institute on Aging of the National Institutes of Health (NIH), entitled "Coordinating Center for Genetics and Genomics of Alzheimer's Disease (CGAD)" and "Replication and Extension of ADSP Discoveries in African-Americans." These newly awarded contracts are part of a global initiative to detect genetic factors associated with Alzheimer's disease risk in an effort to identify new targets for drug development.

"We are very excited to expand our work at the HIHG on the genetics of Alzheimer's disease," said Margaret Pericak-Vance, Ph.D., director of the HIHG and the Dr. John T. Macdonald Foundation Professor of Human Genetics. "We are at a crucial point in the Alzheimer's Disease Sequencing Project where we have the opportunity to replicate the findings from our Discovery Phase Cohort, moving us closer to new drug target identification. In addition, expanding our research to African Americans, a diverse and underrepresented group in Alzheimer's disease research, in combination with the ADSP efforts, has the potential to hasten translation of these findings into better treatments and potential preventions while making these therapies available to a broader section of the Alzheimer community."

The first project, CGAD, represents the replication phase for the presidentially-mandated Alzheimer's Disease Sequencing Project (ADSP). In this project, whole exome sequence (the genes that make protein) data from more than 11,000 individuals (6,000 Alzheimer's disease patients and 5,000 cognitively intact individuals) and whole genome sequence data (3.3 billion base pairs each) from 500 individuals in families with multiple individuals with Alzheimer's disease are being analyzed.

Pericak-Vance is principal investigator of the NIA-funded Consortium for Alzheimer's Sequence Analysis (CASA), part of the ADSP. The newly-funded grant, CGAD, represents the ADSP replication phase following up on results from the ADSP discovery analysis. CGAD is a $10.8 million five-university effort led by collaborators at the University of Pennsylvania in partnership with the University of Miami, Case Western Reserve University, Boston University, Columbia University and University of Indiana. The University of Miami efforts for CGAD will be co-led by Pericak-Vance and Eden Martin, Ph.D., director of the Center for Genetic Epidemiology and Statistical Genetics at the HIHG and professor of human genetics in the Dr. John T Macdonald Foundation Department of Human Genetics.

"Our initial discovery phase taught us much about handling 'big data' and harnessing the wealth of information in one's genomic sequence to identify gene targets for diseases such as Alzheimer's disease," said Martin. "Our replication efforts will build on this work and help, not only to validate findings, but to extend them to other racial and ethnic groups, thus expanding the scope of the science and potential impact of findings to patient populations."

The second funded research project, "Replication and Extension of ADSP Discoveries in African Americans," is co-led at the University of Miami by Pericak-Vance and Gary Beecham, Ph.D., director of research at HIHG and assistant professor in the Dr. John T Macdonald Foundation Department of Human Genetics. Despite steady improvement in the overall health of the United States, individuals within underserved groups continue to be more vulnerable to lapses in care and are at increased risk for health problems. African Americans have a higher prevalence and incidence of dementia and AD than non-Hispanic white individuals, however, there have been considerably few studies that include this population. Thus, as new therapies are developed, these underserved groups may not benefit from these discoveries. The new funding will expand the HIHG's work on the genetics of Alzheimer's that affects diverse populations. Through this project, investigators at the HIHG will conduct a genomic study of Alzheimer's disease in African Americans by enrolling African American families that have multiple individuals with the disease. Since patient ascertainment is a key element in this project, HIHG staff will continue to educate diverse communities about the disease, warning signs and symptoms related to the disease and promote participation from individuals diagnosed with Alzheimer's and their families.

The African American grant is a nearly $4 million collaborative project with three other universities: Goldie Byrd, Ph.D., will lead the project at NCA&T University; Jonathan Haines, Ph.D., at Case Western Reserve University; and Richard Mayeux, M.D., MS, at Columbia University.

Other Miller School investigators include Jeffery M. Vance, M.D., Ph.D., director for the Center for Genomic Education and Outreach (C-GEO) at HIHG and professor of human genetics and neurology; Holly Cukier, Ph.D., research assistant professor of neurology; Michael Cuccaro, Ph. D., Associate Director of C-GEO at HIHG and Associate Professor in the DHG and the Department of Psychology; Larry Deon Adams, HIHG Project Manager, Kara Hamilton, HIHG statistical analyst, and Nancy Joseph, HIHG Research Support Coordinator.

"Replication and Extension of ADSP Discoveries in African-Americans" was awarded under NIA grant number U01AG052410, CASA is supported under UG19AG047133 and CGAD is supported under grant U54AG052427.

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