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New Breakthroughs for Alzheimer's?

December 15, 2005
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Researchers with the University of Florida and the California Institute of Technology have developed a new strain of genetically modified mice that allow scientists to examine the potential usefulness of new therapies for Alzheimer's disease.

The development, reported in a recent edition of the journal PloS Medicine, has helped scientists evaluate the brain's ability to repair one of Alzheimer's hallmark lesions - senile plaque.

These plaques occur when enzymes - substances that cause or speed up chemical reactions - create protein fragments that are called beta amyloid, also known as Abeta. The fragments clump together with other molecules, clogging the spaces between cells and damaging parts of the brain used for memory and decision-making.

The mice were genetically engineered by scientists to respond to a type of therapy designed to stop the production of the damaging amyloid.

According to David Borchelt, Ph.D., a professor of neuroscience at the McKnight Brain Institute of University of Florida: "We can stop the disease from getting worse in these mice, but we can't reverse it.

How the Brain Works
"Although it is possible that human brains repair damage better than mouse brains, the study suggests that it may be difficult to repair lesions once they've formed."

The need to recognize and treat Alzheimer's patients at the first signs of impairment will be important to the success of potential treatments, says Joanna Jankowsky, Ph.D., a biologist at the California Institute of Technology and first author of the paper: "The popular expectation was that, once the contribution to the plaque went away, the plaque itself would dissolve.

"But it may be similar to coronary artery disease - once plaques start to occlude your arteries, it's not clear that stopping the contribution to growth will make the occlusion break up and go away."

Alzheimer's disease is a form of dementia, a brain disorder that trips up the thoughts, memory and language skills of about 4.5 million Americans. It is not a normal outcome of aging, but the disease does affect about 5 percent of men and women ages 65 to 74, according to the National Institute on Aging.

Nearly half of people 85 and older may have it.

Reverse the Symptoms?
Drugs collectively known as secretase inhibitors are currently in development, and are based on the theory that lowering production of Abeta could halt progression of the disease and perhaps reverse symptoms.

In the first experiments to test the idea in a mouse model, scientists engineered 25 mice to carry two artificial genes, one designed to continuously produce Abeta in their brains and the other to turn off Abeta production. The "off switch" was triggered when the antibiotic tetracycline was added to the animals' food.

With Abeta production in full swing, the brains of mice at six months of age were filled with plaques. When the researchers switched the system off, they found the existing plaques did not grow or spread, but they did not go away, either.

Scientists from the Johns Hopkins School of Medicine, the Mayo Clinic Jacksonville and the National Cancer Institute made major contributions to the research.

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