ScienceDaily (Nov. 13, 1998) — An enzyme that fails to get activated in patients with Alzheimer's disease may play a broader role in normal memory, report USC neuroscientists Zoltan Tokes, Ph.D., and Giselle Lim, Ph.D., at the meeting of the Society for Neuroscience in Los Angeles today.

In 1996, Tokes showed that an enzyme produced by neurons in the hippocampus, a region of the brain important in short term memory and learning, was inactive in Alzheimer's patients.

The inactivity of the enzyme persisted despite a greater amount of the enzyme, called matrix metalloproteinase-9 or MMP-9, being produced in the neurons of people with Alzheimer's. In healthy brains, investigators believe MMP-9 acts to help digest and clear away proteins that may accumulate around the nerve cells and interfere with their function.

The team hypothesized that the inactive MMP-9 found in Alzheimer's patients might explain the build-up of characteristic protein plaques found in these patients. Now, Tokes and colleagues say that the inactivated enzyme might also explain the loss of memory seen in Alzheimer's patients.

Tokes' collaborators, cancer researchers Zena Werb and Tienna Vu at U.C. San Francisco, created a transgenic mouse that was missing a gene for the MMP-9 enzyme. Using a standard memory assay, Tokes and Lim then showed that the "knockout" mice had impaired memory. The finding supports the USC team's idea that inactivity of the MMP-9 enzyme may contribute to the memory impairment seen in patients with Alzheimer's.

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