PHILADELPHIA – The International Genomic Alzheimer’s Project (IGAP) analyzed information from more than 94,000 individuals and found new information on the underlying causes of Alzheimer disease (AD), including five new genes that increase risk for the disease. Their findings were published this week in Nature Genetics.
The study, which was funded in part by the National Institute on Aging (NIA) and other components of the National Institutes of Health (NIH), follows results from a 2013 study, and used more genetic data than any other study of AD to date. In addition to confirming the known association of 20 genes with risk of Alzheimer’s and identifying the new risk genes, the team identified which cellular pathways might be implicated in the disease process.
The IGAP team is led by Gerard Schellenberg, PhD, a professor of Pathology and Laboratory Medicine from the Perelman School of Medicine at the University of Pennsylvania, with lead authors, Brian Kunkle and Margaret Pericak-Vance from the University of Miami, and Benjamin Grenier-Boley and Jean-Charles Lambert from INSERM in Lille, France.
“The Alzheimer's Disease Genetics Consortium at Penn, one of the key components of IGAP, has helped organize a significant portion of the data used in this work,” Schellenberg said. “Only by pooling our data and working with international collaborators can we make these significant discoveries that we hope will pave the way for Alzheimer’s disease prevention and treatments.”
The researcher’s analysis implicated the immune system, lipid metabolism, and amyloid precursor protein (APP) metabolism. Mutations in the APP gene have been shown to be directly related to early-onset Alzheimer’s. The present study, using data from late-onset Alzheimer’s patients, suggests that gene variants affecting APP and amyloid beta protein processing are associated with both types of AD. In addition, for the first time, the study implicated a genetic link of AD to tau-binding proteins. Taken together, the findings suggest that therapies developed by studying subjects with early-onset disease could also be applied to the late-onset form of Alzheimer’s.
Penn investigators Adam Naj and Li-San Wang are also leads on the Penn IGAP and ADGC teams. The research was funded by the NIH (AG032984, AG036528, AG21886, AG041689, AG016976, AG049505, AG056270).
For more information about this study and the research collaboration, visit: the University of Miami Miller School of Medicine and NIA News.
Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, excellence in patient care, and community service. The organization consists of the University of Pennsylvania Health System and Penn’s Raymond and Ruth Perelman School of Medicine, founded in 1765 as the nation’s first medical school.
The Perelman School of Medicine is consistently among the nation's top recipients of funding from the National Institutes of Health, with $550 million awarded in the 2022 fiscal year. Home to a proud history of “firsts” in medicine, Penn Medicine teams have pioneered discoveries and innovations that have shaped modern medicine, including recent breakthroughs such as CAR T cell therapy for cancer and the mRNA technology used in COVID-19 vaccines.
The University of Pennsylvania Health System’s patient care facilities stretch from the Susquehanna River in Pennsylvania to the New Jersey shore. These include the Hospital of the University of Pennsylvania, Penn Presbyterian Medical Center, Chester County Hospital, Lancaster General Health, Penn Medicine Princeton Health, and Pennsylvania Hospital—the nation’s first hospital, founded in 1751. Additional facilities and enterprises include Good Shepherd Penn Partners, Penn Medicine at Home, Lancaster Behavioral Health Hospital, and Princeton House Behavioral Health, among others.
Penn Medicine is an $11.1 billion enterprise powered by more than 49,000 talented faculty and staff.