Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Draining away brain's toxic protein to stop Alzheimer's

14.08.2007
Scientists are trying a plumber’s approach to rid the brain of the amyloid buildup that plagues Alzheimer’s patients: Simply drain the toxic protein away.

That’s the method outlined in a paper published online August 12 by Nature Medicine. Scientists from the University of Rochester Medical Center show how the body’s natural way of ridding the body of the substance is flawed in people with the disease. Then the team demonstrated an experimental method in mice to fix the process, dramatically reducing the levels of the toxic protein in the brain and halting symptoms. The team is now working on developing a version of the protein that could be tested in people with the disease.

The approach doesn’t take direct aim at the pathology that is ubiquitous in the Alzheimer’s patients’ brains, where amyloid-beta forms a toxic plaque. Instead, researchers take an indirect approach, focusing not on the brain but rather on a protein that sops up amyloid-beta in the body, where it’s regarded as harmless. The scientists found that if they increase the body’s ability to soak up amyloid, the brain responds, causing levels of the substance in the brain – the real target – to plummet.

“There is a dynamic equilibrium between the levels of amyloid-beta in the blood and in the brain,” said neuroscientist Berislav Zlokovic, M.D., Ph.D., the leader of the team. “If we are able to lower the levels of amyloid-beta circulating in blood by sequestering more of it there, then the brain should follow and lower its levels too. This is exactly what we found.”

The team concentrated its efforts around a protein known as sLRP (soluble low-density lipoprotein receptor-related protein). The team discovered that in healthy people, the protein binds to and neutralizes anywhere from 70 to 90 percent of the amyloid-beta that is circulating in the body.

The team also found that sLRP is doing only a fraction of the job in Alzheimer’s patients that it does in healthy people. Levels of sLRP in people with Alzheimer’s were about 30 percent lower than in healthy people, and the sLRP that was present was almost three times as likely to be damaged compared to the same protein in healthy people. As a result, the Alzheimer’s patients had on average three to four times as much loose, unbound amyloid-beta floating in their bloodstreams – high levels that would likely also be reflected in the brain.

Zlokovic’s group decided to try to reduce amyloid-beta levels in the body by synthesizing an altered, super-potent form of sLRP that binds amyloid-beta more efficiently than natural sLRP. In blood samples from patients with Alzheimer’s disease, the modified version of sLRP, known as LRP-IV, soaked up and virtually eliminated amyloid-beta. The compound had an even more dramatic effect in mice with features of Alzheimer’s disease: LRP-IV lowered the levels of amyloid-beta in their brains by 85 to 90 percent. The mice that received the compound also had improved learning and memory compared to mice that did not receive LRP-IV, and they had 65 percent more blood flow in their brains in response to brain stimulation – a flick of their whiskers.

The team is now working with a company created by Zlokovic, Socratech, to create a form of LRP-IV that could be tested in people. Zlokovic hopes to have such a product ready for testing within two years.

Zlokovic, a scientist widely recognized for demonstrating that blood vessels, blood flow, and the blood-brain barrier are all central to the development of Alzheimer’s disease, likens the new approach to how statins help people with heart disease. Statins lower excess cholesterol in the bloodstream before the cholesterol can glom onto a blood vessel and cause problems with blood flow; in the same way, LRP-IV lowers amyloid-beta and indirectly lowers levels of amyloid-beta in the brain.

It was more than a decade ago that Zlokovic first identified LRP, a molecule that acts like an escort service in the brain, shuttling amyloid-beta out of the brain and into the body. The amyloid plaques that speckle the brains of Alzheimer’s patients are a hallmark of the disease, and where they come from and how to get rid of them has long been a focus of scientists.

“We used to think that Alzheimer’s disease was a problem with the production of too much amyloid-beta, but it’s become clear in recent years that the problem is with faulty clearance of amyloid-beta,” said Zlokovic, professor of Neurosurgery and Neurology and director of the Frank P. Smith Laboratory for Neuroscience and Neurosurgery Research. “We aren’t really talking about massive amounts of amyloid-beta. Even a small malfunction in the elaborate system that carries it into or out of the brain could lead, over years, to accumulate in amounts that damage the brain.”

Tom Rickey | EurekAlert!
Further information:
http://www.urmc.rochester.edu

More articles from Health and Medicine:

nachricht 3D images of cancer cells in the body: Medical physicists from Halle present new method
16.05.2018 | Martin-Luther-Universität Halle-Wittenberg

nachricht Better equipped in the fight against lung cancer
16.05.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg

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: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Research reveals how order first appears in liquid crystals

23.05.2018 | Life Sciences

Space-like gravity weakens biochemical signals in muscle formation

23.05.2018 | Life Sciences

NIST puts the optical microscope under the microscope to achieve atomic accuracy

23.05.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>