Adapted from the Washington University School of Medicine in St. Louis
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 Dr. John G. Csernansky and Dr. Hongxin Dong. 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.
When they widened their search for molecules released in the mouse brain by stress, the scientists identified one called corticotropin-releasing factor (CRF), which is linked to increased levels of brain cell communication.
When they directly placed CRF in the mouse brain, amyloid beta levels rose immediately. Mice given a CRF blocker and then stressed did not display increased amyloid beta.
"There are very few known environmental risk factors for Alzheimer's disease," says senior author Dr. David Holtzman. "Head trauma increases risk, higher education lowers it. Stress may be another environmental factor that increases risk."
Holtzman, Csernansky and their colleagues are intrigued by the possibility that drugs that block CRF or reduce anxiety may provide a new way to decrease amyloid beta and eventually delay or prevent Alzheimer's disease.
Alzheimer’s Disease Research, a program of the American Health Assistance Foundation, is proud to have previously funded Dr. Csernansky and to have Dr. Holtzman as a member of its Scientific Review Committee.