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Aug 13, 2007

Researchers Find that the Brain Follows the Body’s Lead in Clearing Amyloid Beta

  • Scientists from the University of Rochester Medical Center say that they have found how the body’s natural way of getting rid of amyloid is flawed in people with Alzheimer’s disease. They also demonstrated an experimental method in mice to fix the process.

    Instead of targeting amyloid beta buildup in the brain, the researchers focused on a protein that absorbs the protein in the body, where it’s regarded as harmless. They report finding that if they increase the body’s ability to absorb amyloid, the brain responds, causing levels of the substance in the brain to plummet.

    The research team, led by Berislav Zlokovic, M.D., Ph.D., concentrated its efforts on a protein known as sLRP (soluble low-density lipoprotein receptor-related protein). They discovered that in healthy people the protein binds to and neutralizes anywhere from 70% to 90% of amyloid beta that is circulating in the body.

    The scientists also found that sLRP is doing only a fraction of the job in people with Alzheimer’s. Levels of sLRP in patients were about 30% lower than in healthy people. Additionally, the sLRP 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 loose, unbound amyloid beta floating in their bloodstreams—high levels that would likely also be reflected in the brain, the researchers hypothesize.

    Dr. Zlokovic’s group synthesized a super-potent form of sLRP that binds amyloid beta more efficiently than natural sLRP. In blood samples from patients with Alzheimer’s disease, this compound, known as LRP-IV, soaked up and virtually eliminated amyloid beta. In mouse models, the compound lowered the levels of amyloid beta in their brains by 85% to 90%. The mice that received the compound also had improved learning and memory compared to mice that did not.

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

    The research appears online in August 12 issue of Nature Medicine.



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