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Production of key Alzheimer's protein monitored for first time in humans

rates stay balanced, causing the overall amount of Abeta in the central nervous system to remain constant. In the healthy volunteers who were the first test subjects, Bateman found the production and clearance rates were the same. He is now applying the technique to individuals with Alzheimer's disease.

Researchers are developing Alzheimer's drugs that either decrease Abeta production or increase its clearance, Bateman notes, and the new test could be very important in determining which approach is most effective.

Prior to the new test, the only way to assess the effectiveness of a new Alzheimer's drug was to follow the mental performance of patients receiving the treatment over many months or years.

"This new test could let us directly monitor patients in clinical trials to see if the drug is really doing what we want it to do in terms of Abeta metabolism," Bateman says. "If further study confirms the validity of our test, it could be very valuable for determining which drugs go forward in clinical trials and at what doses."

The test also may be useful in diagnosis of Alzheimer's prior to the onset of clinical symptoms, which occurs after Alzheimer's has inflicted widespread and largely irreversible damage to the brain.

"We hope to study whether we can develop ways to identify potential Alzheimer's patients on the basis of a metabolic imbalance between Abeta synthesis and clearance rates," Bateman says.

The test combines technologies that have been available for some time but only through recent technical and procedural advances has become sufficiently sensitive. Via an intravenous drip, scientists give test subjects a form of the amino acid leucine that has been very slightly altered to label it. Inside the leucine are carbon atoms with 13 neutrons and protons in their nucleus instead of the more common 12 neutrons and protons--in scientific parlance, carbon 13 instead of carbon 12.

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Source:Washington University School of Medicine


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