Psychological Stress–Induced Immune Response and Risk of Alzheimer's Disease in Veterans from Operation Enduring Freedom and Operation Iraqi Freedom |
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| Institution: | 1. Harry S. Truman Memorial Veterans Hospital, US Department of Veterans Affairs, Columbia, MO, USA;2. Department of Neurology, School of Medicine, University of Missouri, Columbia, MO, USA;3. Center for Translational Neuroscience, School of Medicine, University of Missouri, Columbia, MO, USA;4. Phelps Health, Rolla, MO, USA;1. School of Medicine, Boston University, Boston, MA, USA;2. Health Effects Laboratory Division, Center for Disease Control and Prevention – National Institute for Occupational Safety and Health, Morgantown, WV, USA;3. School of Public Health, Boston University, Boston, MA, USA;1. Marcella Niehoff School of Nursing, Department of Health Promotion, Loyola University Chicago, Health Science Division, 2160 South First Ave., Maywood, IL 60153, United States;2. Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Health Science Division, 2160 South First Ave., Maywood, IL 60153, United States;1. Neuroscience Center, HiLIFE, University of Helsinki, Viikinkaari 4, FIN-00014, Helsinki, Finland;2. Research Institute of Marine Drugs and Nutrition, Key Laboratory of Aquatic Product Processing and Safety, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China;3. Department of Psychology and Neuroscience, Dalhousie University, 1355 Oxford St, Life Sciences Centre, Halifax, Nova Scotia B3H4R2, Canada;4. Institute of Translational Biomedicine, St Petersburg State University, St Petersburg 199034, Russia;5. Ural Federal University, Ekaterinburg 620002, Russia;6. ZENEREI Research Center, Slidell, LA 70458, USA;7. Department of Neurosciences, Alzheimer Research Laboratory, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA;8. A.I.Virtanen Institute for Molecular Sciences, University of Eastern Finland, Neulaniementie 2, 70150, Kuopio, Finland;9. Zhejiang University-University of Edinburgh Joint Institute, 718 East Haizhou Rd., Haining, Zhejiang 314400, China;10. Psychiatry Research Centre, Beijing Huilongguan Hospital, Peking University, Beijing 100096, China |
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| Abstract: | PurposePsychological stress is a significant health problem in veterans and their family members. Traumatic brain injury (TBI) and stress lead to the onset, progression, and worsening of several inflammatory and neurodegenerative diseases in veterans and civilians. Alzheimer's disease (AD) is a progressive, irreversible neuroinflammatory disease that causes problems with memory, thinking, and behavior. TBIs and chronic psychological stress cause and accelerate the pathology of neuroinflammatory diseases such as AD. However, the precise molecular and cellular mechanisms governing neuroinflammation and neurodegeneration are currently unknown, especially in veterans. The purpose of this review article was to advance the hypothesis that stress and TBI-mediated immune response substantially contribute and accelerate the pathogenesis of AD in veterans and their close family members and civilians.MethodsThe information in this article was collected and interpreted from published articles in PubMed between 1985 and 2020 using the key words stress, psychological stress, Afghanistan war, Operation Enduring Freedom (OEF), Iraq War, Operation Iraqi Freedom (OIF), Operation New Dawn (OND), traumatic brain injury, mast cell and stress, stress and neuroimmune response, stress and Alzheimer's disease, traumatic brain injury, and Alzheimer's disease.FindingsChronic psychological stress and brain injury induce the generation and accumulation of beta-amyloid peptide, amyloid plaques, neurofibrillary tangles, and phosphorylation of tau in the brain, thereby contributing to AD pathogenesis. Active military personnel and veterans are under enormous psychological stress due to various war-related activities, including TBIs, disabilities, fear, new environmental conditions, lack of normal life activities, insufficient communications, explosions, military-related noise, and health hazards. Brain injury, stress, mast cell, and other immune cell activation can induce headache, migraine, dementia, and upregulate neuroinflammation and neurodegeneration in veterans of Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn. TBIs, posttraumatic stress disorder, psychological stress, pain, glial activation, and dementia in active military personnel, veterans, or their family members can cause AD several years later in their lives. We suggest that there are increasing numbers of veterans with TBIs and stress and that these veterans may develop AD late in life if no appropriate therapeutic intervention is available.ImplicationsPer these published reports, the fact that TBIs and psychological stress can accelerate the pathogenesis of AD should be recognized. Active military personnel, veterans, and their close family members should be evaluated regularly for stress symptoms to prevent the pathogenesis of neurodegenerative diseases, including AD. |
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| Keywords: | afghanistan war alzheimer's disease amyloid plaque iraq war psychological stress traumatic brain injury |
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