Alzheimer's linked to excess of one protein

December 17, 1992|By Newsday

New evidence that simple overproduction of one protein can cause Alzheimer's disease was reported yesterday by a research team in Boston.

The work involved inserting a mutant gene into normal human cells, which then produced the damaging protein in abundance. The mutant gene came from a Swedish family plagued by a rare inherited form of Alzheimer's disease.

Dennis Selkoe, a neurologist who is a member of the team, said, "The most exciting part of this is that these Swedish cells can be used in the test tube to screen drugs" that might slow production of the damaging protein.

In addition, the experiment provided the first direct evidence of what goes wrong biochemically that leads to the symptoms of Alzheimer's disease, which afflicts about 4 million Americans.

"The mutation simply causes a marked increase in production of the amyloid beta protein, which over time leads to the buildup of plaques," the large accumulations of the protein seen in autopsies of brain tissue of Alzheimer's patients, Dr. Selkoe said. "This strongly supports the idea that amyloid is the culprit."

Dr. Selkoe, an Alzheimer's researcher at Brigham and Women's Hospital in Boston, said the mutant gene from Sweden makes an abnormal form of the amyloid beta protein, which piles up in lumps in brain tissues.

"By just a very simple single DNA mutation, you can get from 600 to 800 percent more amyloid beta protein produced by these cells," he said. That, and other evidence, suggests that overproduction of amyloid beta is an early step in a cascade of events that leads to the memory-erasing disorder.

Dr. Selkoe and eight colleagues reported their work in this week's issue of Nature.

He said six or seven different mutations in the amyloid-making gene have been found by different research groups, and all produce amyloid accumulation.

John Growdon, a neurologist at Massachusetts General Hospital in Boston, said Dr. Selkoe's results are "exceptionally important and interesting. The name of the game is to get a better understanding of the factors that control amyloid deposition."

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