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Genetics
Genetic Link Discovered for Late Onset Alzheimer's
The long arm of human chromosome 10 harbors a gene that could powerfully predispose people to develop late onset Alzheimer's disease, Massachusetts General Hospital researchers have found. Although they have not yet identified the actual gene, they have evidence that it could be more potent than previous risk factors.
"Whatever the gene is, the robustness of the link says it's probably going to be a major late onset Alzheimer's gene. So we need to find it," says Rudy Tanzi. Photo by Graham Ramsay
"I wouldn't be surprised if this turns out to be a bigger Alzheimer gene than
APOE4," said Rudolph Tanzi, HMS professor of neurology and director of MGH's Genetics and Aging Unit. He and his colleagues report their findings in the Dec. 22
Science. Lars Bertram, HMS research fellow in neurology, is lead author on the paper.
Bertram, Tanzi, and their colleagues located the genetic hotspot by comparing the genetic makeup of Alzheimer's patients and their unaffected siblings in 435 families enrolled in the National Institute of Mental Health database. Using standard statistical methods along with a novel family-based association program, they focused on six genetic markers in the vicinity of the gene for insulin-degrading enzyme, which is believed to help degrade the Alzheimer's disease-causing protein A-beta. Siblings with Alzheimer's were found to be significantly more likely to carry particular versions of two of the genetic markers. One of these markers appears to be located quite close to the actual disease-causing mutation.
Tanzi believes that the findings could help usher in a new era of Alzheimer's treatment in which people are genetically screened and then treated based on their constellation of predisposing genetic factors.
"Once we finally have reliable pathogenic gene changes, we can screen people for these genetic factors—with genetic and psychological counseling and with legal safeguards—and then use that genetic profile to predict who is going to get the disease, with what probability, by what age, and what is the best drug for them based on their genetic profile," he said.
—Misia Landau
Copyright 2001 by the President and Fellows of Harvard College
