Four new genes for Alzheimer's disease risk identified

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.