Group items tagged

In contrast, each of the new genes increases risk by no more than 10 to 15 percent; for that reason, they will not be used to decide if a person is likely to develop Alzheimer’s. APOE, which is involved in metabolizing cholesterol, “is in a class of its own,” said Dr. Rudolph Tanzi, a neurology professor at Harvard Medical School and an author of one of the papers.

But researchers say that even a slight increase in risk helps them in understanding the disease and developing new therapies. And like APOE, some of the newly discovered genes appear to be involved with cholesterol.

The other paper is by researchers in Britain, France and other European countries with contributions from the United States. They confirmed the genes found by the American researchers and added one more gene.

The American study got started about three years ago when Gerard D. Schellenberg, a pathology professor at the University of Pennsylvania, went to the National Institutes of Health with a complaint and a proposal. Individual research groups had been doing their own genome studies but not having much success, because no one center had enough subjects. In an interview, Dr. Schellenberg said that he had told Dr. Richard J. Hodes, director of the National Institute on Aging, the small genomic studies had to stop, and that Dr. Hodes had agreed. These days, Dr. Hodes said, “the old model in which researchers jealously guarded their data is no longer applicable.”

So Dr. Schellenberg set out to gather all the data he could on Alzheimer’s patients and on healthy people of the same ages. The idea was to compare one million positions on each person’s genome to determine whether some genes were more common in those who had Alzheimer’s. “I spent a lot of time being nice to people on the phone,” Dr. Schellenberg said. He got what he wanted: nearly every Alzheimer’s center and Alzheimer’s geneticist in the country cooperated. Dr. Schellenberg and his colleagues used the mass of genetic data to do an analysis and find the genes and then, using two different populations, to confirm that the same genes were conferring the risk. That helped assure the investigators that they were not looking at a chance association. It was a huge effort, Dr. Mayeux said. Many medical centers had Alzheimer’s patients’ tissue sitting in freezers. They had to extract the DNA and do genome scans.

“One of my jobs was to make sure the Alzheimer’s cases really were cases — that they had used some reasonable criteria” for diagnosis, Dr. Mayeux said. “And I had to be sure that people who were unaffected really were unaffected.”

Meanwhile, the European group, led by Dr. Julie Williams of the School of Medicine at Cardiff University, was engaged in a similar effort. Dr. Schellenberg said the two groups compared their results and were reassured that they were largely finding the same genes. “If there were mistakes, we wouldn’t see the same things,” he added. Now the European and American groups are pooling their data to do an enormous study, looking for genes in the combined samples. “We are upping the sample size,” Dr. Schellenberg said. “We are pretty sure more stuff will pop out.”