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Miller-McCune

Thursday, December 4, 2008
Today in Mice

Promising New Research on Alzheimer's Disease

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Beta-amyloid plaque is found in the brains of Alzheimer's patients.

Researchers have known for several years that early removal of plaque in the brain, which damages nerve cells and inflames tissue, is the key to treating Alzheimer's disease. But the natural blood-brain barrier, which prevents most substances from entering the brain from the bloodstream, complicates treatment.

Recently, researchers at Cedars-Sinai Medical Center in Los Angeles who were studying the problem in mice didn't get the results they were looking for - in fact, they came to the exact opposite conclusion - but are hoping their unexpected findings may suggest a new strategy against the disease.

The study targeted the build-up of sticky brain plaque, using immune system cells from other parts of the body. In the mice, these cells became attracted to the plaque and were able to cross the blood-brain barrier, which significantly reduced plaque deposits and caused the mice to perform better on behavioral tests.

"Attempts to develop therapies for Alzheimer's disease have been difficult because most rely on getting a therapeutic molecule or antibody across the blood-brain barrier. If results from our study in mice engineered to develop Alzheimer's-like dementia are supported by studies in humans, we may be able to develop a drug that could be introduced into the bloodstream to cause peripheral immune cells to target the amyloid plaques," said Terrence Town, lead author of the article.

Attempts to attack the plaque have been thwarted not only by the blood-brain barrier, but by the fact that the brain is not conducive to strong immune responses. Town and his colleagues thought Alzheimer's would only worsen if they blocked a certain molecule on immune cells, called macrophages, outside the brain.

"What we found was the exact opposite -- which gave us the opportunity to learn something new about the biology of Alzheimer's disease," Town said. "When we behaviorally tested the mice, we found they were doing better by some measures. And when we looked at the brains of these mice, we noticed that the amyloid plaques were strikingly reduced -- by as much as 90 percent by some methods."

Further tests confirmed that macrophages from the bloodstream were entering the brain and scrubbing away the plaque.

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