Chronic stress has been shown to increase the risk of a number of negative health outcomes, including heart disease, cancer and dementia. The means by which stress contributes to the development of these conditions, however, aren’t as clear. But now, researchers from the University of Florida may have an answer to the question of how chronic stress contributes to the development of Alzheimer’s disease, the most common form of dementia.
In a study conducted on a mouse model and human cells, researchers found that stress exposure triggers the release of a hormone in the brain that boosts the production of protein fragments known beta-amyloids, which in turn initiate the brain degeneration that ultimately leads to Alzheimer’s disease. The research, published in The EMBO Journal, strengthens the idea of a link between stress and Alzheimer’s disease, a disorder believed to stem from a mix of genetic, lifestyle and environmental factors.
“[This study] provides detailed insight into the stress mechanisms that might promote at least one of the Alzheimer’s pathologies,” the authors wrote.
The research comes at an important time, as the disease is becoming more common but the causes remain poorly understood. More than 5 million Americans have Alzheimer’s and one in eight older Americans live with the disease, according to the Alzheimer’s Association. Moreover, the prevalence of the disease is expected to triple over the next 30 years.
Figuring out the non-genetic factors that heighten the risk of Alzheimer’s disease is especially challenging, and the new study is one step in a long process of looking at the effects of stress and other environmental factors, according to the researchers. It could also point the way to a novel treatment approach in the future, the team said.
Stress hormone triggers enzyme activity to increase beta-amyloid production
For the study, the UF 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.
The results showed that the stressed mice had a greater abundance of 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 and cause the cognitive impairments that characterize the disease.
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.
To better understand how CRF increases the amount of Alzheimer’s-related proteins, researchers then treated human neurons with CRF. That caused a significant increase 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,” the authors wrote.
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, the researchers said. One possible solution — blocking the CRF receptor that initiates the stress-induced process that generates Alzheimer’s-related proteins — didn’t work. Researchers are now looking at an antibody that could be used to block the stress hormone directly, the team said, though they admit this approach will be challenging.
“These softer, non-genetic factors that may confer risk of Alzheimer’s disease are much harder to address,” they wrote. “But we need more novel approaches in the pipeline than we have now.”
The research points towards not only to new possibilities for targeted treatments and medications, but also to the importance of healthy lifestyles in reducing the risk of developing Alzheimer’s and other forms of dementia.
In addition to regulating stress levels, experts say the most important steps you can take to reduce your risk of dementia are to eat a healthy diet, engage in regular physical activity, maintain a healthy weight, limit alcohol consumption, and avoid smoking. According to a study published earlier this year, one in three cases of Alzheimer’s disease could be prevented by adopting healthier lifestyle behaviors.