St. Louis, June 4, 2007 Scientists revealed in November 2006 that stress increases production in mice of a brain peptide critical to Alzheimer's disease. Now the same group has shown that blocking a different brain peptide slows the stress-induced increase, opening a new door to treatment. Researchers from Washington University School of Medicine in St. Louis report the results online this week in the Proceedings of the National Academy of Sciences.

Studies of humans and animals have suggested that stress may increase risk of Alzheimer's disease, but the new research is among the first studies to elaborate the basic biomolecular mechanisms that may underlie this increased risk.

The results build on earlier findings from coauthors John G. Csernansky, M.D., the Gregory B. Couch Professor of Psychiatry and professor of neurobiology, and Hongxin Dong, Ph.D., instructor in psychiatry. Using mice genetically modified to model human Alzheimer's disease, Csernansky and Dong showed that raising them under isolated conditions in smaller cages accelerated the deposition of brain plaques and declines in cognitive ability.

Brain plaques are believed to be a primary cause of the memory loss and other mental damage inflicted by Alzheimer's disease. They are mostly comprised of a peptide known as amyloid beta, so researchers immediately suspected that stress was increasing amyloid beta levels. But because there are other factors that can accelerate plaque build-up, they needed to test the link.

For that new test, scientists used a technique known as microdialysis to monitor amyloid beta levels in the brains of mice exposed to the same stressors: isolation and smaller cages.

"Stress remarkably elevated soluble amyloid beta levels in the spaces between brain cells," says senior author David Holtzman, M.D., the Andrew B. and Gretchen P. Jones Professor and head of the Department of Neurology. "But we didn't know based on those initial experiments if it was
'"/>

Contact: Jim Dryden
jdryden@wustl.edu
314-286-0110
Washington University School of Medicine
4-Jun-2007