4 new genes for Alzheimer's disease risk identified by Alzheimer's disease consortium

(Press-News.org) CHICAGO — In the largest study of its kind, researchers from a consortium of 44 universities and research institutions in the United States, including Rush University Medical Center, 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.

The findings, published in the April issue of Nature Genetics, offer new insight into the underlying causes of Alzheimer's disease.

"This is a major advance in the field thanks to many scientists across the country working together over several years," said Dr. David Bennett, director of the Rush Alzheimer's Disease Center. "These findings add key information needed to understand the causes of Alzheimer's disease and should help in discovering approaches to its treatment and prevention."

In the study, the Alzheimer's Disease Genetics Consortium conducted a genetic analysis of more than 11,000 people with Alzheimer's disease and nearly the same number of elderly people who have no symptoms of dementia.

The Rush Alzheimer's Disease Center contributed clinical and genomic data from more than 1,500 participants in two of its premier cohort studies, the Rush Religious Orders Study and the Rush Memory and Aging Project.

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.

Until recently, only four genes associated with late-onset Alzheimer's have been confirmed. The gene for apolipoprotein E-e4, APOE-e4, identified over 15 years ago, has the largest effect on risk. Over the past two years, three additional genes have been identified, including CR1, CLU, and BIN1. The present study adds another four — MS4A, CD2AP, CD33, and EPHA1 — and contributes to identifying and confirming two other genes, BIN1 and ABCA7, thereby doubling the number of genes known to play a role in Alzheimer's disease.

The identification of new genes associated with Alzheimer's provides major clues about the causes of the disease, information that is critical for drug discovery. Currently available treatments are only marginally effective.

In addition, genetic studies can help researchers understand the pathogenic mechanisms that begin in the brain long before symptoms appear, eventually destroying large parts of the brain and causing the complete loss of cognitive abilities. One primary goal of genetic studies is to help identify who is likely to develop the disease, which will be important when preventive measures become available.

Currently, Alzheimer's genetics researchers are collaborating on an even larger, similar study. The Alzheimer's Association in the U.S. and the Foundation 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 present study was supported by the National Institute on Aging (NIA), 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 Alzheimer's Disease Alzheimer's disease is a progressive neurodegenerative disorder for which there is no treatment. Available drugs only marginally affect disease severity and progression. 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 three to five percent at 65-69 years increasing to about 30 to 40 percent at 85-89 years. In the United States, 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 United States, Alzheimer's disease cases will increase to 8-16 million by 2050, with one in 45 Americans affected. Alzheimer's disease will add enormously to future U.S. health care costs.

About Rush University Medical Center Rush is a not-for-profit academic medical center comprising Rush University Medical Center, Rush University, Rush Oak Park Hospital and Rush Health. Rush University, with more than 1,730 students, is home to one of the first medical schools in the Midwest, and one of the nation's top-ranked nursing colleges. Rush University also offers graduate programs in allied health and the basic sciences.