A new study – funded by the National Institutes of Health and the US Department of Veterans Affairs -- with a mouse model and human cells demonstrates that a stress-coping hormone released by the brain boosts the production of protein fragments called amyloid beta. These fragments trigger the brain degeneration that leads to Alzheimer’s disease. The results shed light on the possible relationship between stress and Alzheimer’s disease, which is believed to stem from a mix of genetic, lifestyle and environmental factors. The findings strengthen the idea of a connection between stress and Alzheimer’s disease.
According to Todd Golde, professor of neuroscience at the University of Florida, “It adds detailed insight into the stress mechanisms that might promote at least one of the Alzheimer’s pathologies.”
It is especially challenging to determine the non-genetic factors that heighten the risk of Alzheimer’s disease. The study helps to look at the effects of stress and other environmental factors and offers guidance for new treatment approaches in the future.
Stress triggers the release of the hormone corticotrophin releasing factor, or CRF, in the brain, and that increases production of amyloid beta. When amyloid beta collects in the brain, it starts a complex degenerative cascade that leads to Alzheimer’s disease.
In the new study mice exposed to acute stress had more of the Alzheimer’s-related protein in their brains than mice in a control group. Additionally, the stressed mice had more of a specific kind of amyloid beta, one that has a particularly significant role in the development of Alzheimer’s disease, according to a report in the EMBO Journal. For a greater understanding of how CRF increases the amount of Alzheimer’s-related proteins, the researchers treated human neurons with CRF, triggering a considerable increase in the amyloid proteins involved in Alzheimer’s disease.
The experiments show more about the mechanics of a likely relationship between stress and Alzheimer’s disease. CRF causes the enzyme gamma secretase to increase its activity, which causes more of the Alzheimer’s-related protein to be produced, according to Golde.
Researchers believe that modifying environmental factors such as stress is an easier approach to warding off Alzheimer’s disease than modifying the genes that cause the disorder. Because blocking the CRF receptor that initiates the stress-induced process that generates Alzheimer’s-related proteins did not work, the researchers are contemplating an antibody that may be used to block the stress hormone directly.
Golde summarized, “These softer, non-genetic factors that may confer risk of Alzheimer’s disease are much harder to address, but we need more novel approaches in the pipeline than we have now.”