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Stress and Alzheimer’s Disease: A Hormonal Connection

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ReceStressntly, findings were published in the Journal of Alzheimer’s Disease that may help explain why people who are susceptible to stress are at more risk of developing Alzheimer’s and why — increasingly — we are finding evidence that physical activity, which reduces stress levels, may reduce the chances of developing Alzheimer’s.

It is widely believed that the stress hormone corticotrophin-releasing factor (CRF) may have a protective effect on the brain, including the memory changes brought on by Alzheimer’s. CRF is associated with the production of stress and is found in high levels in people experiencing various forms of anxiety. Normal levels of CRF are beneficial to the brain, keeping cognitive abilities sharp and aiding the survival of nerve cells. Interestingly, previous studies have shown that people with Alzheimer’s disease have a reduced level of CRF.

In this paper, researchers used an experimental drug to prevent CRF from binding to the brain receptor called CRFR1 in mice with Alzheimer’s that were free from memory impairments, therefore blocking its effects. They discovered that the mice had an abnormal stress response with reduced anxiety and impaired learning. Moreover, they found that interrupting the hormone from binding to the CRFR1 receptor blocked the improvement of memory normally promoted by exercise. However, in mice with Alzheimer’s disease, moderate exercise restored the normal function of the CRF system allowing its memory enhancing effects.

The effects of stress on the brain have been studied for decades—ever since the initial work by Canadian endocrinologist Hans Selye, who coined the term”stress.”  Selye himself went on to publish 33 books and more than 1,600 scientific articles, almost all of them on the subject of stress.

This study of biological stress and its effects is a science that continues to make advances today by connecting stress to illness, including Alzheimer’s disease. Certainly, more research is needed to map out the functions of CRF and CRFR1 in normal aging as well as in Alzheimer’s, and the findings published here are compelling for such work.

Thanks for reading.

Michael S. Rafii, M.D., Ph.D.

Director, Memory Disorders Clinic
Associate Medical Core Director, Alzheimer’s Disease Cooperative Study
University of California San Diego

Pardon et al. Corticotropin-Releasing Factor Receptor 1 Activation During Exposure to Novelty Stress Protects Against Alzheimer’s Disease-Like Cognitive Decline in AßPP/PS1 Mice, Journal of Alzheimer’s Disease.

This post originally appeared in Alzheimer’s Insights, an ADCS Blog.

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