Stress and Alzheimer’s – A Pilot Grant for Dr. Dong
Dr. Hongxin Dong, MD. Ph.D., Assistant Professor of Psychiatry and Behavioral Sciences, along with Dr. John Csernansky, MD, Lizzie Gilman Professor and Chair of Psychiatry and Behavioral Sciences at Northwestern Feinberg School of Medicine, Dr. Louis Muglia, MD, Ph.D., Edward Claiborne Stahlman Professor of Pediatrics, Professor of Molecular Physiology and Biophysics, Vice Chair for Research Affairs in Pediatrics at Vanderbilt University Medical Center, and Dr. David Holtzman, MD, Andrew B. and Gretchen P. Jones Professor and Chair of Neurology and Molecular Biology & Pharmacology at Washington University School of Medicine are working together to study the relationship between stress and Alzheimer’s disease and the mechanisms by which corticotrophin-releasing factor (CRF), a critical stress factor, affect β-amyloid by creating a triple transgenic mouse model that conditionally overexpresses CRF and amyloid precursor protein (APP).
This innovative project is funded by the Cognitive Neurology and Alzheimer’s Disease Center (CNADC) at Northwestern University as a pilot award and will serve as the first step to applying for a National Institute of Aging (NIA) grant this fall.
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common form of dementia in the United States. Although the cause of this disease is not clear, some risk factors, which increase the chances of developing AD, have been identified. Stress, which is a common phenomenon in our daily life, has been considered as one of these risk factors. Previous research reported that patients with AD had increased levels of stress hormones (cortisol) and changes in the hypothalamic-pituitary-adrenal (HPA) axis as compared to healthy individuals. Also, people who are more prone to distress are more likely to develop AD than their more carefree counterparts.
Recently, Drs. Dong and Csernansky’s lab and the other groups have reported that Tg2576 mice, a mouse model of AD, show an increased production of β-amyloid under stressful conditions. Furthermore, they have determined that increases in the release of CRF may play a key role in linking stress with increases in plaque deposits.
In this project, Dr. Dong and her colleagues plan to cross-breed Tg2576 mice with a second transgenic mouse model that overproduces CRF in the brain. This mouse model will provide direct information as to whether an increase in CRF in the brain could increase the production of plaque. Finally, they propose to determine whether CRF receptor antagonists can prevent the effects of stress on the disease progression in Tg2576 mice. These studies should improve our understanding of the biological relationships between stress, the brain’s stress system, and the disease process of AD.
A description of the research activities at Dr. Hongxin Dong’s Laboratory of Translational Neurobiology are on its webpage.