Stress Hormone May Contribute to Amyloid-Beta in Alzheimer's

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Stress Hormone May Contribute to Amyloid-Beta in Alzheimer's
Stress Hormone May Contribute to Amyloid-Beta in Alzheimer's

Alzheimer's disease is believed to stem from a combination of genetic, lifestyle, and environmental factors, all of which contribute to the various pathologies associated with the aging disease. Now, new research indicates that a stress hormone may contribute to the production of amyloid-beta buildup in the brain.

The findings, which were published in The EMBO Journal, could point to a definitive environmental factor responsible for Alzheimer's disease progression and could influence future treatment.

"These softer, non-genetic factors that may confer risk of Alzheimer's disease are much harder to address," said researcher Todd E. Golde, MD, PhD. "But we need more novel approaches in the pipeline than we have now."

In a mouse model, researchers from the University of Florida found that acute stress caused the release of the hormone corticotrophin releasing factor (CRF), boosting activity of gamma secretase which increased the production of amyloid-beta. Mice exposed to acute stress were found to have more amyloid-beta buildup than those in a control group. Upon treating human neurons with CRF, the researchers observed a significant increase in amyloid production.

Researchers attempted to modify the effect of stress by blocking the CRF receptor, however results were unsuccessful. They are now focusing on an antibody that can block the stress hormone directly.

“These data collectively link CRF to increased Aβ through γ‐secretase and provide mechanistic insight into how stress may increase AD risk,” the authors wrote. “They also suggest that direct targeting of CRF might be necessary to effectively modulate this pathway for therapeutic benefit in AD, as CRFR1 antagonists increase Aβ and in some cases preferentially increase Aβ42 via complex effects on γ‐secretase.”

Reference

  1. Park HJ et al. EMBO J. 2015; doi:10.15252/embj.201488795.
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