Inhibition of CRF prevented stress-induced build up of amyloid beta.

Researchers from Washington University School of Medicine found that inhibiting corticotropin-releasing factor (CRF), which is linked to increased levels of brain cell communication, prevented stress-induced amyloid beta buildup. 

Previously, researchers believed that stress may increase the risk of Alzheimer’s disease, but the mechanism was unknown. In order to see if stress increases amyloid beta levels, scientists used a technique known as microdialysis to monitor the 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 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.”

The researchers utilized a quicker way to cause stress: temporarily restrain mice from moving. Three hours of restraint led to a 30% increase in amyloid beta levels.

This encouraged researchers to start looking for molecules that might be enabling this rapid change. Stress hormones produced by the adrenal gland were natural suspects. In mice, that meant corticosterone, the mouse equivalent of the human hormone cortisol. But a large dose of corticosterone didn’t cause a similar rapid change in amyloid beta levels. When they widened their search for molecules released in the mouse brain by stress, the scientists identified CRF.

When they directly placed CRF in the mouse brain, amyloid beta levels rose immediately. However, mice given a CRF blocker and then stressed did not display increased amyloid beta.

the discovery is reported in the June 4 advance online edition of the Proceedings of the National Academy of Sciences.

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