In the largest study of its kind, researchers from a consortium led by the University of Pennsylvania School of Medicine, Boston University School of Medicine and the University of Miami 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 Boston, led by Lindsay A. Farrer, PhD, and Miami, led by Margaret A. Pericak-Vance, 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.
"The skyrocketing prevalence and financial and societal costs of Alzheimer's disease will soon undermine the delivery of healthcare worldwide," said Farrer. "That gives our national research enterprise added incentive to act quickly and boldly to make new discoveries."
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.
About Boston University School of Medicine
Alzheimer's disease is a progressive neurodegenerative disorder for which there are no prevention methods. Available drugs only marginally affect disease severity and progression, making Alzheimer's disease effectively untreatable. Alzheimer's disease invariably progresses to complete incapacitation and death over a period of several years. The risk for Alzheimer's disease increases exponentially with age with a prevalence of 3-5% for 65-69 years increasing to ~30-40% for 85-89 years. In the United State, 3-5 million people have Alzheimer's disease, costing $24.6 billion per year for health care and an additional $36.5 billion per year for lost productivity, worker absenteeism, and replacement. The cost in human suffering is incalculable. There are 35 million people with Alzheimer's disease world-wide. As the population ages, in the US, Alzheimer's disease cases will increase to 8-16 million by 2050, with 1 in 45 Americans affected. Alzheimer's disease will add enormously to future US health care costs. Identification of genes that contribute to Alzheimer's disease risk and that influence other characteristics of Alzheimer's disease will reveal basic pathogenic mechanisms, identify proteins and pathways for drug development, and provide genetic methods for determining people at greatest risk for when preventative measures become available.
About Boston University School of Medicine
Originally established in 1848 as the New England Female Medical College, and incorporated into Boston University in 1873, Boston University School of Medicine today is a leading academic medical center with an enrollment of more than 700 medical students and more than 800 masters and PhD students. Its 1,246 full and part-time faculty members generated more than $335 million in funding in the 2009-2010 academic year for research in amyloidosis, arthritis, cardiovascular disease, cancer, infectious disease, pulmonary disease and dermatology among others. The School is affiliated with Boston Medical Center, its principal teaching hospital, the Boston and Bedford Veterans Administration Medical Centers and 16 other regional hospitals as well as the Boston HealthNet.
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