Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


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

Test could improve diagnosis and treatment, help scientists better understand causes of dementia

Media assistance: Michael Purdy (314) 286-0122 Science is now poised to answer an important and longstanding question about the origins of Alzheimer's disease: Do 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 from the Alzheimer's Disease Research Center (ADRC) at 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. According to the authors, the new testing process opens a valuable window into the genesis of Alzheimer's disease that, in addition to helping scientists better understand the origins of the condition, will likely help them improve its diagnosis and treatment.

The scientists' results will be published online on June 25 by Nature Medicine.

High levels of Abeta in the brain are a hallmark of Alzheimer's disease and believed to be a pivotal cause of the condition. Tests that measure Abeta levels in the cerebrospinal fluid have been available for some time. However, those fixed assessments of Abeta gave no indication of whether the flood of Abeta in patient's brains came from an increase in the mechanisms that make the protein or a reduction in the processes that regularly clear it from the brain.

Because Alzheimer's symptoms take many years to develop, some researchers had assumed that the creation and clearance rates for Abeta were very slow. But the initial test of the new technique, applied to six healthy volunteers, suggests the opposite.

"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."

Ideally, the production and clearance 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.

"Normally only about 1.1 percent of the carbon atoms in our bodies are carbon 13--the vast majority is carbon 12," Bateman notes. "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 labeled leucine and incorporate it into the new copies they make of Abeta and other proteins. Scientists take periodic samples of the subjects' cerebrospinal fluid through a lumbar catheter, purify the Abeta from the samples and then use a device known as a mass spectrometer to determine how much of the Abeta includes carbon-13-labeled leucine.

Tracking the rise of the percentage of Abeta with labeled leucine over time gives scientists the subject's Abeta production rate. When the percentage of Abeta containing labeled leucine plateaus, scientists remove the IV drip supplying the labeled leucine. Periodic sampling of the patients' CSF continues, allowing scientists to get a measurement of how quickly the nervous system clears out the labeled Abeta. In the first test subjects, the test procedure lasted for 36 hours.

Other research groups have expressed an interest in applying the new test to Alzheimer's research and to other neurological disorders such as Huntington's disease.

Michael C. Purdy | EurekAlert!
Further information:

More articles from Health and Medicine:

nachricht Resolving the mystery of preeclampsia
21.10.2016 | Universitätsklinikum Magdeburg

nachricht New potential cancer treatment using microwaves to target deep tumors
12.10.2016 | University of Texas at Arlington

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Resolving the mystery of preeclampsia

21.10.2016 | Health and Medicine

Stanford researchers create new special-purpose computer that may someday save us billions

21.10.2016 | Information Technology

From ancient fossils to future cars

21.10.2016 | Materials Sciences

More VideoLinks >>>