In a leap forward in the search for a cause of Alzheimer's tTC disease, researchers have discovered that a pinpoint mutation in a single gene can cause this progressive neurological illness.
The discovery, by Dr. John Hardy of St. Mary's Hospital in London and his colleagues, is the first gene for Alzheimer's disease that has been found.
Although there are likely to be others that can cause the disease, the discovery of this one will allow investigators to narrow their search for causes and treatments for the disease.
Alzheimer's, which afflicts an estimated 2 million Americans and is the nation's fourth leading cause of death, is characterized by a gradual loss of memory and reasoning, and eventually by severe disorientation. There is no treatment for the disease.
The finding is important for two reasons. It advances understanding of Alzheimer's disease by resolving a debate about whether a substance that accumulates in the brains of Alzheimer's patients is a cause of the disease or merely a byproduct.
The defect now discovered is in the gene that directs cells to produce this substance, a component of nerve cells called amyloid protein. And the finding of the defect in Alzheimer's patients but not in healthy individuals indicates that amyloid protein is indeed a cause of the disease.
Second, the search for treatments can therefore now be focused on methods for removing the buildup of amyloid protein. Though such methods may lie far off, at least researchers will now have a strategy to guide them.
Dr. Hardy and his colleagues have found a distinctive mutation in the gene that specifies the amyloid protein, a crucial component of nerve cells. They found the mutation in members of two unrelated families who have Alzheimer's disease.
As further evidence that the mutation in the amyloid gene can cause Alzheimer's disease, Dr. Hardy and his colleagues reported that they did not find the amyloid gene mutation in people who did not have Alzheimer's disease. Their paper will be published in Thursday's issue of the British journal Nature.
There are likely to be other genes that cause Alzheimer's disease because it is already known that genes for the disease can lie on at least two different chromosomes.
But it is also possible, researchers said, that these different genes bring on the disease in the same way, by causing the accumulation of amyloid fragments in the brain.
Researchers are also uncertain whether all or only some Alzheimer's disease is inherited. If some cases occur by chance, there may also be an infection or environmental cause that could, possibly, be traced back to accumulations of the same protein fragments.
"It really is important," said Dr. Dennis Selkoe, an Alzheimer's disease researcher at Brigham and Women's Hospital in Boston. "I'm quite excited about it, and a lot of other people are, too."
Dr. Rudy Tanzi, an Alzheimer's disease researcher at the Massachusetts General Hospital, agreed, calling the finding a "breakthrough."
Alzheimer's disease, which afflicts at least one in five Americans by age 85, has baffled generations of investigators since it was described in 1901. It is characterized by a progressive and unrelenting death of neurons in areas of the brain that are used for memory and reasoning and, eventually, areas that control the personality.