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Increased Risk of Aging-Related Neurodegenerative Disease after Traumatic Brain Injury

Barker, Sarah, Paul, Bindu, Pieper, Andrew·2023·Biomedicines
DOI 10.3390/biomedicines11041154PMC PMC10135798
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Abstract

Traumatic brain injury (TBI) survivors frequently suffer from chronically progressive complications, including significantly increased risk of developing aging-related neurodegenerative disease. As advances in neurocritical care increase the number of TBI survivors, the impact and awareness of this problem are growing. The mechanisms by which TBI increases the risk of developing aging-related neurodegenerative disease, however, are not completely understood. As a result, there are no protective treatments for patients. Here, we review the current literature surrounding the epidemiology and potential mechanistic relationships between brain injury and aging-related neurodegenerative disease. In addition to increasing the risk for developing all forms of dementia, the most prominent aging-related neurodegenerative conditions that are accelerated by TBI are amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Parkinson’s disease (PD), and Alzheimer’s disease (AD), with ALS and FTD being the least well-established. Mechanistic links between TBI and all forms of dementia that are reviewed include oxidative stress, dysregulated proteostasis, and neuroinflammation. Disease-specific mechanistic links with TBI that are reviewed include TAR DNA binding protein 43 and motor cortex lesions in ALS and FTD; alpha-synuclein, dopaminergic cell death, and synergistic toxin exposure in PD; and brain insulin resistance, amyloid beta pathology, and tau pathology in AD. While compelling mechanistic links have been identified, significantly expanded investigation in the field is needed to develop therapies to protect TBI survivors from the increased risk of aging-related neurodegenerative disease.

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Sorted by citations

Authors
Barker, S., Paul, B., & Pieper, A.
Affiliations
  • Center for Brain Health Medicines, Harrington Discovery Institute, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA
  • Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21211, USA
ORCID
Paul, Bindu
Venue
Biomedicines
Publisher
MDPI AG
Published
2023-04-11
Volume
11
Issue
4
Pages
1154
ISSN
2227-9059
DOI
10.3390/biomedicines11041154
PMC
PMC10135798
Cited by
54
References
32
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)
Funders
  • Case Western Reserve University (I01BX005976, NIH/NIA RO1AG065240, NIH/NIA R01AG074346, NIH/NIGMS RM1 GM142002, NIH/NIA RO1AG066707, NIH/NIA 1 U01 AG073323, NIH/NIA 1 P30 AGO62428-01, 19PABH134580006, NIH/NIA 1R01AG071512, P50 DA044123, NIH 1R21AG073684-01, NIH T32 AG071474, NIH T32 GM007250)
  • Brockman Foundation, Department of Veterans Affairs Merit Award (I01BX005976, NIH/NIA RO1AG065240, NIH/NIA R01AG074346, NIH/NIGMS RM1 GM142002, NIH/NIA RO1AG066707, NIH/NIA 1 U01 AG073323, NIH/NIA 1 P30 AGO62428-01, 19PABH134580006, NIH/NIA 1R01AG071512, P50 DA044123, NIH 1R21AG073684-01, NIH T32 AG071474, NIH T32 GM007250)
  • Elizabeth Ring Mather &amp; William Gwinn Mather Fund (I01BX005976, NIH/NIA RO1AG065240, NIH/NIA R01AG074346, NIH/NIGMS RM1 GM142002, NIH/NIA RO1AG066707, NIH/NIA 1 U01 AG073323, NIH/NIA 1 P30 AGO62428-01, 19PABH134580006, NIH/NIA 1R01AG071512, P50 DA044123, NIH 1R21AG073684-01, NIH T32 AG071474, NIH T32 GM007250)
  • S. Livingston Samuel Mather Trust (I01BX005976, NIH/NIA RO1AG065240, NIH/NIA R01AG074346, NIH/NIGMS RM1 GM142002, NIH/NIA RO1AG066707, NIH/NIA 1 U01 AG073323, NIH/NIA 1 P30 AGO62428-01, 19PABH134580006, NIH/NIA 1R01AG071512, P50 DA044123, NIH 1R21AG073684-01, NIH T32 AG071474, NIH T32 GM007250)
  • G.R. Lincoln Family Foundation (I01BX005976, NIH/NIA RO1AG065240, NIH/NIA R01AG074346, NIH/NIGMS RM1 GM142002, NIH/NIA RO1AG066707, NIH/NIA 1 U01 AG073323, NIH/NIA 1 P30 AGO62428-01, 19PABH134580006, NIH/NIA 1R01AG071512, P50 DA044123, NIH 1R21AG073684-01, NIH T32 AG071474, NIH T32 GM007250)
  • Wick Foundation (I01BX005976, NIH/NIA RO1AG065240, NIH/NIA R01AG074346, NIH/NIGMS RM1 GM142002, NIH/NIA RO1AG066707, NIH/NIA 1 U01 AG073323, NIH/NIA 1 P30 AGO62428-01, 19PABH134580006, NIH/NIA 1R01AG071512, P50 DA044123, NIH 1R21AG073684-01, NIH T32 AG071474, NIH T32 GM007250)
  • Leonard Krieger Fund of the Cleveland Foundation (I01BX005976, NIH/NIA RO1AG065240, NIH/NIA R01AG074346, NIH/NIGMS RM1 GM142002, NIH/NIA RO1AG066707, NIH/NIA 1 U01 AG073323, NIH/NIA 1 P30 AGO62428-01, 19PABH134580006, NIH/NIA 1R01AG071512, P50 DA044123, NIH 1R21AG073684-01, NIH T32 AG071474, NIH T32 GM007250)
  • Maxine and Lester Stoller Parkinson’s Research Fund (I01BX005976, NIH/NIA RO1AG065240, NIH/NIA R01AG074346, NIH/NIGMS RM1 GM142002, NIH/NIA RO1AG066707, NIH/NIA 1 U01 AG073323, NIH/NIA 1 P30 AGO62428-01, 19PABH134580006, NIH/NIA 1R01AG071512, P50 DA044123, NIH 1R21AG073684-01, NIH T32 AG071474, NIH T32 GM007250)
  • Gordon &amp; Evie Safran (I01BX005976, NIH/NIA RO1AG065240, NIH/NIA R01AG074346, NIH/NIGMS RM1 GM142002, NIH/NIA RO1AG066707, NIH/NIA 1 U01 AG073323, NIH/NIA 1 P30 AGO62428-01, 19PABH134580006, NIH/NIA 1R01AG071512, P50 DA044123, NIH 1R21AG073684-01, NIH T32 AG071474, NIH T32 GM007250)
  • Louis Stokes VA Medical Center resources and facilities (I01BX005976, NIH/NIA RO1AG065240, NIH/NIA R01AG074346, NIH/NIGMS RM1 GM142002, NIH/NIA RO1AG066707, NIH/NIA 1 U01 AG073323, NIH/NIA 1 P30 AGO62428-01, 19PABH134580006, NIH/NIA 1R01AG071512, P50 DA044123, NIH 1R21AG073684-01, NIH T32 AG071474, NIH T32 GM007250)
  • Translational Therapeutics Core of the Cleveland Alzheimer’s Disease Research Center (I01BX005976, NIH/NIA RO1AG065240, NIH/NIA R01AG074346, NIH/NIGMS RM1 GM142002, NIH/NIA RO1AG066707, NIH/NIA 1 U01 AG073323, NIH/NIA 1 P30 AGO62428-01, 19PABH134580006, NIH/NIA 1R01AG071512, P50 DA044123, NIH 1R21AG073684-01, NIH T32 AG071474, NIH T32 GM007250)
  • American Heart Association (I01BX005976, NIH/NIA RO1AG065240, NIH/NIA R01AG074346, NIH/NIGMS RM1 GM142002, NIH/NIA RO1AG066707, NIH/NIA 1 U01 AG073323, NIH/NIA 1 P30 AGO62428-01, 19PABH134580006, NIH/NIA 1R01AG071512, P50 DA044123, NIH 1R21AG073684-01, NIH T32 AG071474, NIH T32 GM007250)
  • Paul Allen Foundation Initiative in Brain Health and Cognitive Impairment (I01BX005976, NIH/NIA RO1AG065240, NIH/NIA R01AG074346, NIH/NIGMS RM1 GM142002, NIH/NIA RO1AG066707, NIH/NIA 1 U01 AG073323, NIH/NIA 1 P30 AGO62428-01, 19PABH134580006, NIH/NIA 1R01AG071512, P50 DA044123, NIH 1R21AG073684-01, NIH T32 AG071474, NIH T32 GM007250)
  • NIH NIDA (I01BX005976, NIH/NIA RO1AG065240, NIH/NIA R01AG074346, NIH/NIGMS RM1 GM142002, NIH/NIA RO1AG066707, NIH/NIA 1 U01 AG073323, NIH/NIA 1 P30 AGO62428-01, 19PABH134580006, NIH/NIA 1R01AG071512, P50 DA044123, NIH 1R21AG073684-01, NIH T32 AG071474, NIH T32 GM007250)
  • Catalyst Award from Johns Hopkins University (I01BX005976, NIH/NIA RO1AG065240, NIH/NIA R01AG074346, NIH/NIGMS RM1 GM142002, NIH/NIA RO1AG066707, NIH/NIA 1 U01 AG073323, NIH/NIA 1 P30 AGO62428-01, 19PABH134580006, NIH/NIA 1R01AG071512, P50 DA044123, NIH 1R21AG073684-01, NIH T32 AG071474, NIH T32 GM007250)
  • The Alzheimer’s Disease Translational Data Science Training Program (I01BX005976, NIH/NIA RO1AG065240, NIH/NIA R01AG074346, NIH/NIGMS RM1 GM142002, NIH/NIA RO1AG066707, NIH/NIA 1 U01 AG073323, NIH/NIA 1 P30 AGO62428-01, 19PABH134580006, NIH/NIA 1R01AG071512, P50 DA044123, NIH 1R21AG073684-01, NIH T32 AG071474, NIH T32 GM007250)
  • Case Western Medical Scientist Training program (I01BX005976, NIH/NIA RO1AG065240, NIH/NIA R01AG074346, NIH/NIGMS RM1 GM142002, NIH/NIA RO1AG066707, NIH/NIA 1 U01 AG073323, NIH/NIA 1 P30 AGO62428-01, 19PABH134580006, NIH/NIA 1R01AG071512, P50 DA044123, NIH 1R21AG073684-01, NIH T32 AG071474, NIH T32 GM007250)

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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

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