Researchers said Friday they had found a genetic defect that appears to cause some cases of Alzheimer's disease, a development that could lead to important new insights into the devastating disease.
The scientists discovered a flaw in a gene for a protein that builds up in Alzheimer's disease victims' brains. The flawed gene seems linked with the disease in two families in which an unusual form of Alzheimer's tends to be inherited.The research needs to be followed up by studies of more families and more patients, and if it is confirmed, scientists said, the defect will probably only be the cause of a small percentage of Alzheimer's disease cases.
But the finding indicates the gene, known as the amyloid precursor protein gene, may be more central to the disease than had been thought, with other forms perhaps being caused by other defects in the same gene or in other genes that interact with it, experts said.
"I think the findings are very significant," said Dr. Kenneth Kosik, a professor of medicine at Harvard Medical School in Boston and a member of the medical and scientific advisory board of the Alzheimer's Disease Association.
"It certainly can lead to a much more concrete way to think about the way the disease originates and open up some ways of doing research that could lead to treatment," he said.
Dr. Peter St. George-Hyslop, an Alzheimer's researcher at the University of Toronto, was more cautious, saying there have been conflicting reports about the role of the amyloid gene in Alzheimer's. "It's interesting but further work needs to be done," he said.
The findings will be published next week in the British journal Nature by an international team of researchers led by Drs. Alison Goate and John Hardy of the St. Mary's Hospital Medical School in London.
Alzheimer's disease is a gradual, irreversible erosion of brain cells that control thought and memory. The disease affects between 2 million and 4 million Americans and usually strikes after age 65, but in a small percentage of cases it typically appears as early as age 35.
Every person has 23 pairs of chromosomes that carry the genetic blueprints for everything from hair color to predisposition to diseases. Scientists previously found evidence a gene associated with some forms of Alzheimer's was located on chromosome 21. But none had been able to find a specific gene or defect that caused any form of the disease.
In the new study, the researchers from England, the University of Wales, Yale University Medical Center in New Haven, Conn., and Duke University in Durham, N.C., worked for about three years to analyze genetic material from families in which the early-onset form of the disease was common.
In two families - one in Britain and one in North Carolina - the researchers found a single change in the coding for the amyloid gene on chromosome 21 that was strongly associated with the disease.
Amyloid tends to accumulate in distinctive abnormal tangles and plaques in the brains of Alzheimer's patients, apparently disrupting brain function.
"I think its importance, if it continues to be true, is that it will be the first cause of Alzheimer's which has been described," Goate said by telephone. "Although it's probably only going to account for a small percentage of cases it has importance for being a known cause of the disase. It's the only known cause."
For the small number of families in which this mutation may cause the disease, the "implications are profound" because it could lead to tests that could predict if they will develop the disease, said Robert Williamson, another one of the researchers.
"For the great majority of people the implications are attention can be focused on the protein that is almost certainly the major player in this disease, and attempts can be made to design drugs that can interfere directly with the deposition of this protein," he said.