New Alzheimer's Gene Discovered
An international research team has identified a major new gene — named SORL1 — that is associated with Alzheimer's disease. Found in four distinct ethnic groups, SORL1 is only the second genetic variant for late-onset Alzheimer's, by far the most common type of Alzheimer's.
The team, made up of researchers from New York City's Columbia University Medical Center, Boston University School of Medicine and the University of Toronto, found that variants in the SORL1 gene were more common in people with late-onset Alzheimer's than in healthy people the same age. These genetic variants appear to alter the normal function of SORL1, resulting in Alzheimer's.
People with the genetic variants may not be producing normal amounts of SORL1, suggesting that this gene has a protective function when working properly. If this is so, then a reduction of SORL1 in the brain increases the likelihood of developing Alzheimer's disease.
An important aspect of these findings, which appear in the January 14, 2007 advance on-line edition of Nature Genetics (February print edition), is that the association between Alzheimer's disease and SORL1 was demonstrated in four distinct ethnic groups: Caribbean-Hispanics, North Europeans, African-Americans and Israeli-Arabs. Many previous studies on the genetics of Alzheimer's used data from mostly white populations of American and European ancestry. In total, the study involved DNA samples from 6,000 volunteers.
"The importance of the finding is that it opens new pathways to explore the cause and as well as potential targets for treatment of this devastating disease," said Columbia University Medical Center's Dr. Richard Mayeux. "SORL1 represents another critical piece of the Alzheimer's disease puzzle. This appears to be the fifth Alzheimer's disease gene, and there are likely to be other important genetic variants that need to be identified before the entire picture is complete."
"Now that we know that variants in SORL1 are associated with late-onset Alzheimer's disease and we know the specific regions of the gene involved, our next step is to determine which of the variants contain the specific disease causing alteration," said Dr. Mayeux.
Another step would be to determine how many cases of late-onset Alzheimer's are caused by these SORL1 variants. Studies are planned to investigate how many Alzheimer's cases are attributable to SORL1. The hope is that this information will lead to accurate screening for this gene.
Alzheimer's disease, which affects 4.5 million Americans, is categorized as either early-onset or late-onset. The early-onset form is rare and tends to affect those between the ages of 30-60. Most cases of early-onset are also genetic. The late-onset form is much more common — accounts for 90 percent of all cases of Alzheimer's — and tends to affect those aged 65 and older. With aging baby boomers, the prevalence of late-onset Alzheimer's is expected to double in the next 25 years.