Alzheimer's research got a major boost with discovery of four new genes that increase the risk of developing that form of dementia later in life. The findings were made by a national consortium that includes a BYU scientist.
Eleven genes have been identified so far as harboring variations that influence risk for Alzheimer's. The researchers believe that together they account for up to 35 percent of the overall risk, said John "Keoni" Kauwe, assistant professor of biology at Brigham Young University and a co-author on the study being published Sunday in the journal Nature Genetics.
The hope is it will open the door to both targeted treatments and ways to predict who will develop Alzheimer's.
"We're getting to the point where we have enough information to come up with treatments in a reasonable time scale," he said. "For a long time, there was not much known about the genetic component of disease, which is tough, because many treatments are developed using genetic information" including pathways within the body. "These findings are giving us the knowledge we need to test new drugs".
Scientists in 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, took blood samples from about 11,000 people who had been diagnosed with Alzheimer's disease and roughly the same number of others of similar age who showed no signs of the disease. Subjects came from 15 centers around the country. Then the University of Pennsylvania did what's called a genome-wide association study, analyzing more than 1 million bits of genetic information from each sample.
"What we identified were a few variants in four genes that gave us a statistically significant ability to predict membership in either case or control groups," said Kauwe.
The consortium, lead by U. Penn's Gerard D. Schellenberg, includes investigators from 44 universities.
"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," Schellenberg said in a release about the study. "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."
The four new genes are called MS4A, CD2AP, CD33 and EPHA1. The researchers also confirmed two others found by other studies: BIN1 and ABCA7.
Three different consortia contributed "confirming data" so that, in all, the genetics of 54,000 individuals were analyzed. And this consortium contributed to an international group that identified a fifth gene. Its findings appear in the same issue of the journal.
Using the four genes, they could guess accurately whether the owner of the genetic material was in the Alzheimer's group or not.
Such an approach is unbiased and effective, Kauwe said. And being able to predict who might develop the disease will be important once prevention or treatment that really works is available. Existing treatments are only "marginally effective," researchers agree.
It isn't known what combination of variants influences risk for the disease the most or even what the combinations mean. But researchers plan to find out.
Kauwe and several collaborators at Utah State University have just been awarded a grant from the Utah Science Technology and Research (USTAR) initiative to look at the 11 genetic variants using 5,000 samples of DNA from the Cache County Study on Memory and Aging to create an estimate of risk. By looking in a population-based sample, they hope to make an "aggregate risk profile", devising a score based on the variants each carries. Then they'll look in the general population to see "how well the combination of these genetic variants predicts disease," he said.
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