PHILADELPHIA – In the largest study of its kind, researchers from a consortium led by the Perelman School of Medicine, the University of Miami, and the Boston University School of Medicine, identified four new genes linked to Alzheimer’s disease. Each gene individually adds to the risk of having this common form of dementia later in life. These new genes offer a portal into what causes Alzheimer’s disease and is a major advance in the field.
The study, conducted by the Alzheimer’s Disease Genetics Consortium, reports genetic analysis of more than 11,000 people with Alzheimer’s disease and a nearly equal number of elderly people who have no symptoms of dementia. Three other consortia contributed confirming data from additional people, bringing the total number of people analyzed to over 54,000. The consortium also contributed to the identification of a fifth gene reported by other groups of investigators from the United States, the United Kingdom, France, and other European countries. The findings appear in the current issue of Nature Genetics.
The study is the result of a large collaborative effort with investigators from 44 universities and research institutions in the United States, led by Gerard D. Schellenberg, PhD, at Penn, with primary analysis sites at Miami, led by Margaret A. Pericak-Vance, PhD, and Boston, led by Lindsay A. Farrer, PhD.
“This is the culmination of years of work on Alzheimer’s disease by a large number of scientists, yet it is just the beginning in defining how genes influence memory and intellectual function as we age. We are all tremendously excited by our progress so far, but much remains to be done, both in understanding the genetics and in defining how these genes influence the disease process,” Schellenberg said.
Until recently, only four genes associated with late-onset Alzheimer's have been confirmed, with the gene for apolipoprotein E-e4, APOE-e4, having the largest effect on risk. The Nature Genetics studies add another four -- MS4A, CD2AP, CD33, and EPHA1 - and contribute to identifying and confirming two other genes, BIN1 and ABCA7, thereby doubling the number of genes known to contribute Alzheimer's disease.
The researchers’ ultimate aims are two fold. First, identification of new Alzheimer’s disease genes will provide major clues as to its underlying cause. Genetic studies can provide new insights into the molecules at the center of the disease. Gaining this type of understanding is critical for drug discovery since the currently available treatments are only marginally effective.
Second, gene discovery of the type highlighted in the Nature Genetics article will contribute to predicting who will develop Alzheimer’s disease, which will be important when preventive measures become available. Knowing these risk genes will also help identify the first disease-initiating steps that begin in the brain long before any symptoms of memory loss or intellectual decline are apparent. This knowledge will help researchers understand the events that lead to the destruction of large parts of the brain and eventually the complete loss of cognitive abilities.
Currently, Alzheimer’s genetics researchers are coming together for an even larger, similar study. The Alzheimer’s Association in the US and the Fondation Plan Alzheimer in France have funded the formation of the International Genomics of Alzheimer’s Project, whose members met for the first time in November 2010 in Paris.
The research published in Nature Genetics was supported by the National Institute on Aging, part of the National Institutes of Health, which includes 29 Alzheimer’s Disease Centers, the National Alzheimer’s Coordinating Center, the NIA Genetics of Alzheimer’s Disease Data Storage Site, the NIA Late Onset Alzheimer’s Disease Family Study and the National Cell Repository for Alzheimer’s Disease. These Centers collect, store and make available to qualified researchers DNA samples, datasets containing biomedical and demographic information about participants, and genetic analysis data.
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.
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