Researchers Try to Drain Away Brain's Toxic Protein to Stop Alzheimer's

by VR Sreeraman on Aug 14 2007 5:04 PM

Researchers are trying to drain out the amyloid build-up that plagues Alzheimer's patients though a plumber's approach.

University of Rochester Medical Centre researchers have shown that the body's natural way of flushing out the substance is imperfect in people suffering from the disease.

The team demonstrated an experimental method in mice to fix the process, by reducing the toxic protein levels in the brain and halting symptoms. The team is trying to develop a version of the protein that could be tested in people with the disease.

"There is a dynamic equilibrium between the levels of amyloid-beta in the blood and in the brain," Nature Medicine quoted neuroscientist Berislav Zlokovic, the leader of the team, as saying.

"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," Zlokovic added.

The team concentrated on sLRP, a soluble low-density lipoprotein receptor-related protein. The team found that in healthy people, the protein binds to neutralise anywhere from 70 to 90 percent of the amyloid-beta that is flowing in the body.

The team also found that sLRP only does a portion of the job in Alzheimer's patients as compared to healthy people.

Zlokovic's group decided to try to reduce amyloid-beta levels in the body by producing a mutated, 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 researchers have now collaborated 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.

"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," Zlokovic.

The research is published in a paper online August 12 by Nature Medicine.