Stress hormone might play a role in Alzheimer’s
Posted by Doug Bennett-Florida on
A new study with a mouse model and human cells shows that a stress-coping hormone released by the brain boosts the production of protein fragments known as amyloid beta that clump together and trigger the brain degeneration that leads to Alzheimer’s disease.
The findings contribute to further understanding the potential relationship between stress and Alzheimer’s disease, a disorder believed to stem from a mix of genetic, lifestyle, and environmental factors and strengthen the idea of a link between stress and Alzheimer’s disease.
“It adds detailed insight into the stress mechanisms that might promote at least one of the Alzheimer’s pathologies,” says Todd Golde, professor of neuroscience at the University of Florida.
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Figuring out the non-genetic factors that heighten the risk of Alzheimer’s disease is especially challenging, and the recent study is one step in a long process of looking at the effects of stress and other environmental factors. It could also point the way to new treatment approaches in the future.Stress causes the release of a hormone called corticotrophin releasing factor, or CRF, in the brain. That, in turn, increases production of amyloid beta. As amyloid beta collects in the brain, it initiates a complex degenerative cascade that leads to Alzheimer’s disease.
For the new study, published in the EMBO Journal, mice exposed to acute stress had more of the Alzheimer’s-related protein in their brains than those in a control group. The stressed mice also had more of a specific form of amyloid beta, one that has a particularly pernicious role in the development of Alzheimer’s disease.
To better understand how CRF increases the amount of Alzheimer’s-related proteins, the researchers then treated human neurons with CRF. That caused a significant increase in the amyloid proteins involved in Alzheimer’s disease.
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The experiments reveal more about the mechanics of a likely relationship between stress and Alzheimer’s disease. The stress hormone, CRF, causes an enzyme known as gamma secretase to increase its activity. That, in turn, causes more of the Alzheimer’s-related protein to be produced, Golde says.Modifying environmental factors such as stress is yet another approach to warding off Alzheimer’s disease, and one that is easier than modifying the genes that cause the disorder.
One possible solution—blocking the CRF receptor that initiates the stress-induced process that generates Alzheimer’s-related proteins—didn’t work. The researchers are now looking at an antibody that could be used to block the stress hormone directly.
“These softer, non-genetic factors that may confer risk of Alzheimer’s disease are much harder to address,” Golde says. “But we need more novel approaches in the pipeline than we have now.”
The National Institutes of Health and the US Department of Veterans Affairs funded the work.
