Duraisamy Kempuraj1, Mohammad Ejaz Ahmed2, Govindhasamy Pushpavathi Selvakumar2, Ramasamy Thangavel2, Sudhanshu P Raikwar2, Smita A Zaheer3, Shankar S Iyer2, Casey Burton4, Donald James4, Asgar Zaheer5. 1. Harry S. Truman Memorial Veterans Hospital, US Department of Veterans Affairs, Columbia, MO, USA; Department of Neurology, School of Medicine, University of Missouri, Columbia, MO, USA; Center for Translational Neuroscience, School of Medicine, University of Missouri, Columbia, MO, USA. Electronic address: duraisamyk@health.missouri.edu. 2. Harry S. Truman Memorial Veterans Hospital, US Department of Veterans Affairs, Columbia, MO, USA; Department of Neurology, School of Medicine, University of Missouri, Columbia, MO, USA; Center for Translational Neuroscience, School of Medicine, University of Missouri, Columbia, MO, USA. 3. Department of Neurology, School of Medicine, University of Missouri, Columbia, MO, USA; Center for Translational Neuroscience, School of Medicine, University of Missouri, Columbia, MO, USA. 4. Phelps Health, Rolla, MO, USA. 5. Harry S. Truman Memorial Veterans Hospital, US Department of Veterans Affairs, Columbia, MO, USA; Department of Neurology, School of Medicine, University of Missouri, Columbia, MO, USA; Center for Translational Neuroscience, School of Medicine, University of Missouri, Columbia, MO, USA. Electronic address: zaheera@health.missouri.edu.
Abstract
PURPOSE: Psychological 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. METHODS: The 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. FINDINGS: Chronic 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. IMPLICATIONS: Per 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.
PURPOSE: Psychological 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. METHODS: The 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. FINDINGS:Chronic 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. IMPLICATIONS: Per 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.
Authors: Duraisamy Kempuraj; Govindhasamy P Selvakumar; Ramasamy Thangavel; Mohammad E Ahmed; Smita Zaheer; Sudhanshu P Raikwar; Shankar S Iyer; Sachin M Bhagavan; Swathi Beladakere-Ramaswamy; Asgar Zaheer Journal: Front Neurosci Date: 2017-12-12 Impact factor: 4.677
Authors: Evan M Lutton; S Katie Farney; Allison M Andrews; Vladimir V Shuvaev; Gwo-Yu Chuang; Vladimir R Muzykantov; Servio H Ramirez Journal: Front Neurol Date: 2019-06-06 Impact factor: 4.003
Authors: Carl-Martin Pethrus; Johan Reutfors; Kari Johansson; Kristian Neovius; Jonas Söderling; Martin Neovius; Gustaf Bruze Journal: PLoS One Date: 2019-02-01 Impact factor: 3.240