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Genetically Engineered Mice Show Characteristic Signs Of Alzheimer's, Could Be Ideal Tool For Testing New Therapies

out treatments to combat these detrimental effects."

The work was conducted by investigators at the Gladstone Institute of Neurological Disease, a major new research enterprise based at the San Francisco General Hospital campus of UCSF. The results are published in the Sept. 1 issue of Proceedings of the National Academy of Sciences U.S.A.

In one experiment, mice had to learn the location of a hidden target in a maze that tests their ability to remember and process spatial information. Similar skills are strongly affected in Alzheimer's patients, who often get lost because they have trouble finding their way home.

ApoE3 mice learned how to find the hidden target with relative ease, whereas their apoE4 counterparts had difficulty with the exercise, and some never found the target at all even after repeated tries. Consistent with the age dependence of Alzheimer's disease, only older apoE4 mice showed deficits in learning and memory, whereas young apoE4 mice were not impaired.

In another experiment, mice were placed in an open field inside a cage, and their movements were monitored with motion sensors. Older apoE4 mice showed much less exploratory curiosity in this test than age-matched apoE3 mice. The investigators speculate that these findings might also relate to Alzheimer's patients, who often lose interest in their environment and abandon activities that once engaged them.

In both experiments, the researchers noticed a distinct difference in behavior between female and male mice, with the females experiencing a higher level of impairment. These results are consistent with clinical studies by other investigators which suggest that apoE4 increases Alzheimer's risk and decreases responsiveness to treatments more strongly in women than in men.

The researchers already have begun to manipulate the levels of apoE4 in the brains of these mice to see what impact these changes might have on their behavior. Mucke said
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Contact: Corinna Kaarlela
corinna@itsa.ucsf.edu
(415) 476-3804
University of California - San Francisco
31-Aug-1998


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