MEDICINE / ALZHEIMER’S DISEASE : Science Zeros In on Suspected Gene

Researchers are close to identifying the gene responsible for an inherited form of Alzheimer’s disease that strikes unusually early, typically about age 45.

The discovery should provide strong new clues about the development of Alzheimer’s, which afflicts as many as 4 million Americans, most of them over age 65.

The new gene, whose approximate location is reported today in the journal Science by a team from the University of Washington, is the third that has been linked to this devastating illness and suggests that the cause of Alzheimer’s may be far more complicated than researchers had believed.

The discovery represents “a new window on the disorder,” said Dr. Gene Cohen, acting director of the National Institute on Aging. “The more windows we have, the more likely we are to see something that is fundamentally critical” in delaying the disease process--which is the ultimate goal of Alzheimer’s research.

“This is a real breakthrough for Alzheimer’s research,” said Dr. Huntington Potter, a neurologist at Harvard University.

The potential identification of the gene also reflects the emerging consensus that Alzheimer’s is genetic in origin and not induced by external factors such as toxins in the environment.

“Five years ago, many questioned whether or not there was a genetic basis for Alzheimer’s disease,” said Dr. Allen Roses, a neurologist at Duke University. “We now know that there are genetic factors involved and different chromosomes and different genes.

“There are very likely other genetic defects not yet discovered that may be responsible for other cases of Alzheimer’s disease,” Roses said. “Closing in on these . . . will require tremendous efforts.”

Alzheimer’s disease is characterized by memory loss, disorientation, depression and deterioration of body functions. It causes about 100,000 deaths annually in the United States, but the time between detection of the disorder and death varies from as little as three years to as long as 20 years. Inherited Alzheimer’s represents a small fraction of the total cases and usually strikes earlier in life than other forms of the disease.

Washington neurologist Dr. Gerard D. Schellenberg and his colleagues at six other institutions screened more than 200 families in which at least two members had Alzheimer’s. The study included nine families in which three or more members had a documented case of the disorder and in which the average age of onset was 45.

Using the techniques of genetic engineering, the researchers found that each person afflicted by Alzheimer’s in eight of these families had a particular set of so-called markers in a narrow region of chromosome 14, one of the 26 sets of chromosomes that constitute the human genetic blueprint. Unaffected family members did not have the markers.

The new finding indicates that the genetic defect that causes the familial Alzheimer’s is located very close to the markers. “We know roughly where the gene is in the chromosome,” Schellenberg said. “The next step is to locate the gene that is actually defective. Once we locate it we can study it and determine what it does normally and what makes it defective in Alzheimer’s disease.”

Previous studies have found genes associated with Alzheimer’s on chromosomes 19 and 21. “No one knows the significance of the finding to the larger population with Alzheimer’s disease,” said Dr. Thomas Bird, another member of the team.

“But in all the families we examined, the symptoms and pathology were the same as in other forms of Alzheimer’s, so we have found some clues to what is going on in the brain of everyone with Alzheimer’s,” he said.