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Effectiveness of mouse breeds that mimic Alzheimer's disease symptoms questioned
Date:8/16/2007

BETHESDA, Md. Scientists have shown that recently developed mouse breeds that mimic the symptoms of Alzheimer's disease (AD) may not be as effective as previously assumed. Sascha Weggen, Professor of Molecular Neuropathology at Heinrich-Heine-University, Duesseldorf, Germany; lead author Eva Czirr, Ph.D. student at the University of Mainz, Germany; and colleagues show in the August 24 issue of the Journal of Biological Chemistry that in some mouse breeds, drugs that had been shown to reduce levels of a toxic protein called amyloid beta had only minor or no effect on these mice.

Testing drugs against AD on animals is not easy because animals dont develop the disease, Weggen says. When using mice, scientists need to artificially induce one or several mutations in the mice and check whether they develop symptoms of the disease that are similar to the human ones. We showed that some of the mice currently bred to develop the disease dont get better when they receive previously tested drugs.

The new study was selected as a Paper of the Week by the journals editors, meaning that it belongs to the top one percent of papers reviewed in significance and overall importance.

Although no cure is yet available for AD a neurodegenerative disorder affecting around 18 million patients worldwide scientists are testing various compounds that could become drugs. Most compounds try to prevent brain proteins called amyloid beta peptides from aggregating and forming plaques, which is a hallmark of the disease.

Amyloid beta peptides result from the breakdown of a protein called amyloid precursor protein (APP) by enzymes called beta-secretase and gamma-secretase. In AD patients, the breakdown of APP molecules is increased, leading to an excess of amyloid beta peptides. To reduce the amount of amyloid beta, chemical compounds are tested for their ability to block gamma-secretase or reduce its activity.

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Contact: Pat Pages
ppages@asbmb.org
301-634-7366
American Society for Biochemistry and Molecular Biology
Source:Eurekalert

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