Genetic researchers from the University of Miami Miller School of Medicine presented findings on a wide range of topics including diversity inclusion, gene discovery and functional analysis of genetic targets at the Alzheimer’s Association International Conference (AAIC) 2021 conference, held recently in Denver.
"AAIC is the premier international scientific meeting for Alzheimer’s disease research in the world and the ability to meet in person once again with colleagues from around the globe has been invaluable," said Margaret A. Pericak-Vance, Ph.D., director, John P. Hussman Institute for Human Genomics (HIHG); Dr. John T Macdonald Foundation Professor of Human Genetics; and executive vice chair, Dr. John T Macdonald Foundation Department of Human Genetics,
"Genomic research’s goal is the identification of new targets for therapy and prevention," she added. "The Hussman Institute houses one of the top Alzheimer’s disease research genomics research groups in the world and our faculty and students presented our work in all facets of genomic studies."
A neurology perspective
Miller School neurologists investigating Alzheimer’s and memory disorders also presented their work at AAIC.
James E. Galvin, M.D., M.P.H., professor of neurology and director of the Miller School’s Comprehensive Center for Brain Health, discussed the importance of taking a multicultural approach to Alzheimer’s disease research.
"The U.S. population is getting older and becoming more diverse, and we need to understand the differences in risks and protective factors," said Dr. Galvin, who has received several grants from the National Institutes of Health to study the disease in diverse U.S. populations.
He also gave a presentation, "ICARE AD-US: Design of a Prospective, Single-Arm, Multicenter, Noninterventional Real-World Study of Aducanumab in the United States," on a nationwide observational study that aims to measure the real-world effectiveness of the drug.
Other topics Dr. Galvin discussed at AAIC included "Associations Between Neighborhood Greenspaces and Cognitive and Brain Volume Measures in Cognitive Normal Older Adults;" “Effective Feature Learning of Multi-modal of Genetic and Neuroimaging Data for Prediction of Future Conversion to Alzheimer’s disease: A Machine Learning Based Study;” and “Employing the Moca-T (Telephone) as a Means of Cognitive Screening in a Rural, Ethically Diverse Population during COVID-19 Restrictions.”
Three Hussman Institute platform presentations were given virtually in a session titled, "Multi-ethnic Genetics of AD." Anthony J. Griswold, Ph.D., research assistant professor, was the session chair and presented a multi-center collaborative study, "Expression Quantitative Trait Loci (eQTL) Analysis in a Diverse Alzheimer Disease Cohort Reveals Ancestry Specific Regulatory Architectures."
Dr. Griswold noted the challenge of applying Alzheimer disease genetic findings to ancestrally admixed populations, such as African Americans and Caribbean Hispanics from Puerto Rico, who are underrepresented in most studies.
After performing RNA sequencing to determine gene expression levels from the blood of 537 individuals with Alzheimer’s disease or cognitively intact controls, they found African Americans, non-Hispanic Whites and Puerto Ricans had both overlapping and unique sequence variants that control gene expression, reflecting admixed European, African and Amerindian ancestries.
“These results underscore the importance of continuing to include diverse populations in genomics and functional studies to identify both unique and shared genetic architecture of Alzheimer’s disease,” he said.
Brian Kunkle, Ph.D., M.P.H., a genetic epidemiologist and research assistant professor, presented a collaborative study on "APOE-Stratified Genome-Wide Association Analysis Identifies Novel Alzheimer Disease Candidate Risk Loci for African Americans."
This meta-analysis of genome-wide association studies for Alzheimer disease in African Americans identified several new potential genetic risk factors for Alzheimer’s disease in populations with African ancestry. Confirmation of these findings in additional studies could provide novel therapeutic targets for AD, according to the researchers.
Farid Rajabli, Ph.D., associate scientist, presented a third multi-center study, "Admixture Mapping Identifies Novel Regions Influencing Alzheimer Disease in African Americans."
The researchers noted that the admixed mapping of genetic ancestry of African Americans (African and European) provides a unique opportunity to identify novel genetic factors associated with AD. They analyzed 10,271 individuals and confirmed a risk-associated region on chromosome 17p13.2. African American individuals have a lower risk of Alzheimer’s disease if they inherited the chromosome 17p13.2 region from their African ancestors versus African American individuals with European ancestry in the region.
The Miller School is a powerhouse in Alzheimer’s and dementia research. Located in South Florida at the gateway to Latin American and the Caribbean, researchers across disciplines are studying a range of Alzheimer’s disease among diverse cultures. In addition to the Hussman Institute and top Alzheimer’s physician-scientists with the Department of Neurology, the Miller School is home to the Comprehensive Center for Brain Health, the Brain Endowment Bank, a leading Alzheimer's research center and one of six designated brain and tissue biorepositories in the U.S.