Traumatic Brain Injury as a Risk Factor for Dementia and Alzheimer Disease: Critical Review of Study Methodologies

Hicks, Amelia J.; James, Amelia C; Spitz, Gershon; Ponsford, Jennie Louise

doi:10.1089/neu.2018.6346

Cited by 38 publications

(30 citation statements)

References 104 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, it has been reported that a spike of tau hyperphosphorylation happens after brain injury 76 and general anesthesia 77 , due likely to acutely diminished phosphatase activities 78 , 79 . Whether this transient tau hyperphosphorylation is related to the positive association between dementia and traumatic brain injury 13 or exposure to general anesthesia 80 remains an open question. Animal studies may provide a clue as to whether R-(−)-apomorphine can be used to neutralize hyperphosphorylated tau following brain injury or general anesthesia exposure, thus reducing the likelihood of AD and ADRD after recovery.…”

Section: Discussionmentioning

confidence: 99%

“…These include viral infection 10 , cerebrovascular diseases, type 2 diabetes, hypertension, obesity, dyslipidemia 11 , and such environmental factors as metals, pesticides, industrial chemicals and air pollutants 12 . Physical injuries to the brain, e.g., traumatic brain injury and chronic traumatic encephalopathy also predispose patients to AD and AD-related dementia (ADRD) 13 . Lastly, certain prescription drugs have been linked to increased risks for AD and dementia, including benzodiazepines 14 , anticholinergic drugs 15,16 and disease-modifying anti-rheumatic drugs (DMARD) 17 .…”

mentioning

confidence: 99%

See 1 more Smart Citation

Hyperphosphorylated tau aggregation and cytotoxicity modulators screen identified prescription drugs linked to Alzheimer's disease and cognitive functions

Liu

Dexheimer

Sui

et al. 2020

Sci Rep

View full text Add to dashboard Cite

The neurodegenerative Alzheimer’s disease (AD) affects more than 30 million people worldwide. There is thus far no cure or prevention for AD. Aggregation of hyperphosphorylated tau in the brain correlates with the cognitive decline of patients of AD and other neurodegenerative tauopathies. Intracerebral injection of tau aggregates isolated from tauopathy brains causes similar pathology in the recipient mice, demonstrating the pathogenic role of abnormally phosphorylated tau. Compounds controlling the aggregation of hyperphosphorylated tau therefore are probable modulators for the disease. Here we report the use of recombinant hyperphosphorylated tau (p-tau) to identify potential tauopathy therapeutics and risk factors. Hyperphosphorylation renders tau prone to aggregate and to impair cell viability. Taking advantage of these two characters of p-tau, we performed a screen of a 1280-compound library, and tested a selective group of prescription drugs in p-tau aggregation and cytotoxicity assays. R-(−)-apomorphine and raloxifene were found to be p-tau aggregation inhibitors that protected p-tau-treated cells. In contrast, a subset of benzodiazepines exacerbated p-tau cytotoxicity apparently via enhancing p-tau aggregation. R-(−)apomorphine and raloxifene have been shown to improve cognition in animals or in humans, whereas benzodiazepines were linked to increased risks of dementia. Our results demonstrate the feasibility and potential of using hyperphosphorylated tau-based assays for AD drug discovery and risk factor identification.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Hyperphosphorylated tau aggregation and cytotoxicity modulators screen identified prescription drugs linked to Alzheimer's disease and cognitive functions

Liu

Dexheimer

Sui

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…These include viral infection (5), cerebrovascular diseases, type 2 diabetes, hypertension, obesity, dyslipidemia, as well as environmental factors such as metals, pesticides, industrial chemicals and air pollutants (6). Physical injuries to the brain, e.g., traumatic brain injury and chronic traumatic encephalopathy also predispose patients to AD and AD-related dementia (ADRD) (7).…”

Section: Introductionmentioning

confidence: 99%

Hyperphosphorylation Renders Tau Prone to Aggregate and to Cause Cell Death

et al. 2020

View full text Add to dashboard Cite

“…68e70 TBIs lead to neurovascular vertigo, ischemia, neurodegeneration, dementia, and AD pathogenesis. 71,72 Delaying or preventing AD risk Although many studies show a link between TBIs and PTSD with AD, some reports indicate that TBIs and PTSD are not risk factors for AD, based on amyloid positron emission tomography scanning, and suggest additional mechanistic studies are needed to confirm this link. 73 Chronic stress is a significant risk factor associated with the pathogenesis of AD.…”

Section: Methodsmentioning

confidence: 99%

Psychological Stress–Induced Immune Response and Risk of Alzheimer's Disease in Veterans from Operation Enduring Freedom and Operation Iraqi Freedom

Kempuraj

Ahmed

Selvakumar

et al. 2020

Clinical Therapeutics

View full text Add to dashboard Cite

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 warrelated 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

show abstract

Traumatic Brain Injury as a Risk Factor for Dementia and Alzheimer Disease: Critical Review of Study Methodologies

Cited by 38 publications

References 104 publications

Hyperphosphorylated tau aggregation and cytotoxicity modulators screen identified prescription drugs linked to Alzheimer's disease and cognitive functions

Hyperphosphorylated tau aggregation and cytotoxicity modulators screen identified prescription drugs linked to Alzheimer's disease and cognitive functions

Hyperphosphorylation Renders Tau Prone to Aggregate and to Cause Cell Death

Psychological Stress–Induced Immune Response and Risk of Alzheimer's Disease in Veterans from Operation Enduring Freedom and Operation Iraqi Freedom

Contact Info

Product

Resources

About