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Draining away brain's toxic protein to stop Alzheimer's
Date:8/13/2007

Levels of sLRP in people with Alzheimers 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 Alzheimers 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.

Zlokovics 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 Alzheimers 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 Alzheimers 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 Alzheimers 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 se
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Contact: Tom Rickey
tom_rickey@urmc.rochester.edu
585-275-7954
University of Rochester Medical Center
Source:Eurekalert

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