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Alzheimer's Mutations Found in Brain Cells

Mon Jul 5, 2004

WASHINGTON (Reuters) - The genetic mutations that lie behind most cases of Alzheimer's disease may be found inside cell powerhouses known as mitochondria, U.S. researchers said on Monday.

They said they found mutations in mitochondrial DNA in 65 percent of patients in a study who died of Alzheimer's, and none of the patients who died of something else.

Their finding, published this week in the Proceedings of the National Academy of Sciences, could help shed light on the most common form of Alzheimer's, which affects more than 4 million people in the United States alone.

Most DNA is carried on the chromosomes. But an important form is found in the mitochondria of cells, which are structures that help provide energy.

Douglas Wallace of the Center for Molecular and Mitochondrial Medicine and Genetics at the University of California at Irvine and colleagues looked at the brains of 23 people who died of Alzheimer's and 40 people who died free of dementia.

They looked especially for mutations in mitochondrial DNA. They found variations of a particular mutation in 65 percent of the brains of Alzheimer's patients and none of the others.

Several mutations have been linked to early-onset Alzheimer's, but it has been difficult to pin down a cause of the most common form, known as late-onset, sporadic Alzheimer's.

The mutations are associated with reductions in the total amount of mitochondrial DNA, Wallace's team said. It could be that they impair energy production in the cells, increase the generation of free radicals that can damage cells, and destroy the connections between brain cells, they said.

Or the mutations could be a symptom rather than a cause.

"The question remains: is the increase in (the mitochondrial DNA) mutations seen in AD brains simply a reflection of accelerated aging, or is it a distinct pathological phenomenon?" they wrote.


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