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.

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Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4.3 billion enterprise.

The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 17 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $392 million awarded in the 2013 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; Chester County Hospital; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Chestnut Hill Hospital and Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2013, Penn Medicine provided $814 million to benefit our community.

ABOUT ALZHEIMER’S DISEASE
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.

 

 

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