A provocative explanation for the rising incidence of Alzheimer’s disease engages stress as a prime risk factor. New research on how the brain responds to stress on a biomolecular level may lead to a new treatment philosophy for the insidious disease.
Studies of humans and animals have suggested that stress may increase risk of Alzheimer’s disease.
Initial studies revealed that stress increases production in mice of a brain peptide critical to Alzheimer’s disease. Now, scientists discover 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.
The results build on earlier findings from coauthors John G. Csernansky, M.D., and Hongxin Dong, Ph.D.
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.
“But we didn’t know based on those initial experiments if it was a chronic effect or a much more immediate effect. If it was more immediate, we thought we might be able to identify some of the brain molecules involved in increasing the levels.”
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.
Prior research has demonstrated an increased communication between brain cells can also contribute to increased amyloid beta.
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,” Holtzman notes.
“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.
Holtzman and his colleagues are also continuing to explore connections between brain cell activity and amyloid beta levels.
Source: Washington University