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Alzheimer's mice betray cognitive drop.

For some Alzheimer's disease researchers, the immediate goal is not to prevent the deadly neurodegenerative disorder, but to create it. They're the ones seeking to craft a mouse model of the disease. With such an animal stand-in, they would have an inexpensive, well-understood organism in which to test drugs and hypotheses about the causes of the affliction.

Making an Alzheimer's mouse isn't easy, however. A number of mouse models have skyrocketed into prominence, only to fizzle under close examination. Now, an older model, unveiled 4 years ago, may be making a comeback.

This genetically engineered strain of mice experiences a decline in learning and memory skills as it ages, researchers report in the June 6 Proceedings of the National Academy of Sciences.

"That is the cardinal feature [of the disease] in humans, and we have replicated it in mice," says Barbara Cordell of Scios Nova, a biotechnology company in Mountain View, Calif.

In 1991, Cordell led a team that created mice whose brains generate larger than normal concentrations of a beta amyloid precursor protein. Many researchers believe that an abnormal buildup of beta amyloid causes the brain cell degeneration characteristic of Alzheimer's disease. To evaluate the behavior of these mice, Scios Nova then collaborated with the Marion Merrell Dow Research Institute in Strasbourg, France.

Their results mark the first time investigators have shown that mice which overproduce beta amyloid suffer cognitive difficulties analogous to those of affected humans.

Ironically, some researchers had dismissed the Scios Nova mice as a model for Alzheimer's. Although diffuse deposits of beta amyloid build up in the brains of these animals, they do not form the dense plaques found in Alzheimer's patients. So researchers continued the search for a mouse model, lately favoring one in which plaques are present (SN: 2/11/95, p.84).

Cordell and her colleagues subjected their mice to more than a dozen different behavioral tests, including some that examined general activity, anxiety, and motor skills. In two of the tests, one of which relies on learning skills and the other on short-term memory, 9- to 12-month-old Alzheimer's mice performed significantly worse than both normal mice and 6-month-old Alzheimer's mice.

The group plans further tests of learning and memory skills, adds Paula M. Moran of Marion Merrell Dow.

Researchers caution, however, that it may prove impossible to create a perfect mouse model. Some crucial areas of the brain that degenerate in Alzheimer's--regions involved in higher learning--do not even exist in the simpler brains of mice, notes Creighton Phelps, director of the Alzheimer's Disease Research Centers at the National Institute of Aging. "Alzheimer's is a human disease. You can only model aspects of it," he says.
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Title Annotation:progress in development of mouse model of Alzheimer's Disease
Author:Travis, John
Publication:Science News
Article Type:Brief Article
Date:Jun 10, 1995
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