December 2, 2009

Mitochondrial enzyme improves cognition in Alzheimer’s mice

Memory and learning improved in mice with Alzheimer's disease that were crossbred with animals that produced large amounts of a potent antioxidant enzyme made in the mitochondria said researchers from Baylor College of Medicine and New York University in a report that appeared in the Proceedings of the National Academy of Sciences.

"This is one of the first reports with so many improvements in cognition in these mice," said Dr. Robia Pautler, assistant professor in the departments of molecular physiology and biophysics, neuroscience and radiology at BCM.

Reduced reactive oxygen

Superoxide dismutase (SOD-2), an enzyme made in the cell's mitochondria, also reduced the levels of superoxide (reactive oxygen) that is implicated in Alzheimer's disease, said Pautler, who did the research in collaboration with Dr. Eric Klann, now of New York University. The two began their collaboration on the neurodegenerative disorder when Klann was at BCM, where he is still an adjunct professor.

Too much amyloid precursor

The Alzheimer's model mice make too much of a protein that is a precursor to amyloid, the protein complexes that form plaques in the brains of people and animals with the disease and are associated with its disabling effects on the ability to think or remember.

In the offspring of the two kinds of mice, the researchers found that high levels of the enzyme superoxide dismutase decreased the amount of superoxide. Even more exciting, in special laboratory tests, the animals did not show the learning and memory deficits found in the Alzheimer's mice.

First report of a beneficial effect

The findings directly link mitochondrial superoxide to the disabling effects of Alzheimer's, the authors said. It also shows that a mitochondrial anti-oxidant enzyme has a beneficial effect, providing new direction for treatment of the neurodegenerative disorder.

"While other anti-oxidant treatments for Alzheimer's disease have not proven effective, we think something more potent might have benefit," said Pautler, who hopes to continue working in that direction.

The decrease in the amount of amyloid plaque found in the brain also was encouraging, she said.

How are they linked?

"We are trying to understand how overexpression of this enzyme contributes to decreased Alzheimer's disease pathology," she said.

She credits post-doc Dr. Cynthia A. Massaad with much of the actual laboratory work in the research. She said she and Klann collaborated on mentoring Massaad, who hoped to gain experience in multiple areas of research.

Technician Taneasha M. Washington also played an important role in the work, she said.

Funding for the work came from the National Institutes of Health, the National Institute of Neurological Disorders and Stroke, the National Heart, Lung and Blood Institute, the National Institute of Aging, the Alzheimer's Association and the American Health Assistance Foundation.


On the Net: