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

Scientists are trying a plumbers approach to rid the brain of the amyloid buildup that plagues Alzheimers patients: Simply drain the toxic protein away.

Thats the method outlined in a paper published online August 12 by Nature Medicine. Scientists from the University of Rochester Medical Center show how the bodys 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 doesnt take direct aim at the pathology that is ubiquitous in the Alzheimers 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 its regarded as harmless. The scientists found that if they increase the bodys 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 Alzheimers patients that it does in healthy peopl
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Contact: Tom Rickey
tom_rickey@urmc.rochester.edu
585-275-7954
University of Rochester Medical Center
12-Aug-2007


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