A Brigham Young University scientist is part of a consortium that, in the largest study of its kind, 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 was conducted by the Alzheimer’s Disease Genetics Consortium, led by the University of Pennsylvania School of Medicine, the University of Miami, and the Boston University School of Medicine. It 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.

John “Keoni” Kauwe, BYU assistant professor of biology, has been involved in this consortium since its planning stages and is a coauthor on the paper. He is also a coauthor on another paper published in the same issue of the journal with similar findings.

“Being involved with this research group and seeing the progress we’ve made in the last 2.5 years, identifying several new genes associated with Alzheimer’s disease, gives me hope,” Kauwe said. “These findings provide the foundation the field needs to see major improvements in the treatment and management of Alzheimer’s disease during my career.”

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.

“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.

“Now that we’ve identified these genes, the next step is to determine what they do and why they are related to Alzheimer’s disease,” BYU’s Kauwe said. “We want to learn how these genetic variants influence gene function to increase risk for the disease.”

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.

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.

(Much of the information in this news release is provided courtesy of the University of Pennsylvania).

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Writer: Kare Kreeger