Study sheds light on how stress may raise risk of Alzheimer's

Previous research has linked stress with increased risk of Alzheimer's disease, but the mechanisms underlying this association have been unclear. Now, researchers from the University of Florida believe they are one step closer to an explanation.

Researchers say stress triggers the release of a hormone that boosts production of a protein in the brain that is involved in the development of Alzheimer's.

In a study published in The EMBO Journal, researchers at the Center for Translational Research in Neurodegenerative Disease at the University of Florida, describe how a hormone released by the brain in response to stress increases production of a protein associated with Alzheimer's development.

The researchers say the study "adds detailed insight into the stress mechanisms that might promote at least one of the Alzheimer's pathologies."

Based on their findings, the team is now investigating a novel Alzheimer's prevention strategy: the use of an antibody that blocks the release of this stress hormone, inhibiting the production of the Alzheimer's-related protein.

Alzheimer's is the leading cause of dementia in the US, affecting around 5.3 million Americans. By 2050, this number is expected to almost triple to 13.8 million.

The most common risk factors associated with Alzheimer's include age, the presence of certain genes and a family history of the disease. However, researchers are increasingly linking stress to onset of the disease.

Stress hormone triggers enzyme activity to increase beta-amyloid production

For their study, the researchers set out to gain a better understanding of the mechanisms that link stress and Alzheimer's by analyzing the brains of mice that had been subject to acute stress, comparing them with the brains of non-stressed mice.

Fast facts about stress

• Stress contributes to around 60% of all human illness and disease
• Around 3 in 4 doctor's visits in the US are for stress-related health conditions
• Stress-related ailments cost the US around $300 billion every year.

The researchers found that the stressed mice had a greater abundance of a protein called beta-amyloid in their brains than the non-stressed mice. It is well established that beta-amyloid accumulates in the brains of people with Alzheimer's, clumping together to form plaques that are believed to disrupt brain cell communication.

Further investigation revealed that stress causes a hormone called corticotrophin releasing factor (CRF) to be released in the brain. This boosts the activity of an enzyme called gamma secretase, which increases production of beta-amyloid.

On applying CRF to human brain neurons in a laboratory dish, the team witnessed a significant rise in beta-amyloid production.

"These data collectively link CRF to increased beta-amyloid through gamma secretase and provide mechanistic insight into how stress may increase AD [Alzheimer's disease] risk," say the authors.

The research team says their findings also point to a potential therapeutic strategy for Alzheimer's; targeting CRF with an antibody in order to lower levels of the stress hormone and, in turn, reduce beta-amyloid production. However, the researchers admit this approach will be challenging.

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.

References:

1.  The stress response neuropeptide CRF increases amyloid‐β production by regulating γ‐secretase activity, Todd E. Golde et al., The EMBO Journal, doi: 10.15252/embj.201488795, published online 11 May 2015, abstract.
2.  University of Florida news release, accessed 18 September 2015 via EurekAlert.
3.  Additional source: Alzheimer's Association, 2015 Alzheimer's disease facts and figures, accessed 18 September 2015.
4.  Additional source: The American Institute of Stress, Stress is killing you, accessed 18 September 2015.