TAMPA, Fla. (Oct. 26, 2000) -- Researchers at the University of South Florida Roskamp Institute have found a new molecule that may be targeted to prevent the adverse immune response that leads to Alzheimer's disease.

Their findings were published in two parts -- Sept. 7 in the Journal of Biological Chemistry and Oct. 15 in the Journal of Neuroscience.

The molecule, CD45, is a receptor on the surface of microglia, cells that support neurons and participate in the brain's immune response.

The researchers showed that triggering CD45 is beneficial because it blocks a very early step in the development of Alzheimer's disease -- microglial activation of the brain's immune system. If unopposed, this immune reaction would result in inflammation and progressive damage to neurons.

The results provide evidence that the brain's immune response is critically involved in the Alzheimer's disease process, perhaps much earlier than inflammation. "Once brain inflammation occurs, it is probably too late for prevention," said Terrence Town, a co-author of both articles.

This may help explain why nonsteroidal anti-inflammatory drugs only partially alleviate symptoms in patients with Alzheimer's disease. A more effective treatment may combine anti-inflammatory drugs with drugs specifically designed to inhibit microglial activation of nerve cell inflammation in the brain, the authors suggest.

The work builds on a previous study published last year in Science, in which the Roskamp researchers helped bolster a cutting-edge theory that the brain's immune system plays a critical role in Alzheimer's disease. The researchers reported that a signaling mechanism called the CD40 receptor-CD40 ligand interaction, when triggered in the brain, results in microglia damage to neurons.

Now, the researchers have discovered that stimulating a specific molecule, CD45, appears to block the harmful consequences of this CD40 signaling system. Furthermore, they demonstrated that when CD45 is deficient in a genetically-engineered mouse model for Alzheimer's disease, microglial activation of the brain's immune response is dramatically increased.

"In summary, where we previously demonstrated that CD40 signaling promotes pathogenic microglial activation, we now show that CD45 signaling opposes this effect," said Jun Tan, M.D., Ph.D. lead author of both reports.

"The next step is to apply these findings to new treatment strategies for Alzheimer's disease," said Michael Mullan, M.D., Ph.D., director of the USF Roskamp Institute. "We are working with the pharmaceutical industry to screen for drugs that will target the brain's immune cells."

---University of South Florida 

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