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New Test to Identify Alzheimer’s Disease – Diagnosis and Determine Effectiveness of Drugs Used to Treat Condition Quickly

June 25th 2006

New Test to Identify Alzheimer’s Disease – Diagnosis and Determine Effectiveness of Drugs Used to Treat Condition Quickly

Brain Scans

Scientists are closer to determining whether Alzheimer’s patients have high levels of a brain protein because they make too much of it or because they can't clear it from their brains quickly enough. Researchers at the Washington University School of Medicine in St. Louis have developed the first safe and sensitive way to monitor the production and clearance rates of amyloid beta peptide (Abeta) in the human central nervous system.

High levels of the beta peptide Abeta in the brain is a hallmark for Alzheimer's disease and is believed to be a pivotal cause of the condition.  Previously researchers had trouble determining whether the body was producing too much of the peptide or was having trouble removing it from the system. 


Tests that measure Abeta levels in the cerebrospinal fluid have been available for some time. "Abeta has the second-fastest production rate of any protein whose production rate has been measured so far," says lead author Randall Bateman, M.D., assistant professor of neurology. "In a time span of about six or seven hours, you make half the amyloid beta found in your central nervous system."

The new test uses an intravenous drip of a form of the amino acid leucine that has been very slightly altered.  The leucine is modified to contain carbon 13, not the usual carbon 12.  "Normally only about 1.1 percent of the carbon atoms in our bodies are carbon 13.  The vast majority is carbon 12," Bateman said. "Physiologically and biochemically, carbon 13 acts just like carbon 12, meaning it won't alter the normal Abeta production and clearance processes and is very safe to use."


Over the course of hours, cells in the brain pick up the contaminated leucine and incorporate it into the new copies of Abeta and other proteins.  When the percentage of Abeta containing laced leucine plateaus, scientists remove the IV drip. 

The test is quick and relatively painless.  Over the next 36 hours, doctors can get a measurement of how quickly the nervous system clears out the “labeled” Abeta.  Prior to this test the only effective way to assess the effectiveness of a new Alzheimer's drug was to follow the mental performance of the patient 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 can also be used in diagnosing Alzheimer’s prior to the onset of the disease. "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.

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