Brain and blood biomarkers of tauopathy and neuronal injury in humans and rats with neurobehavioral syndromes following blast exposure.

Autor: Dickstein DL; Department of Pathology, Uniformed Services University of Health Sciences, 4301 Jones Bridge Rd, Bethesda, MD, 20814, USA.; Center for Neuroscience and Regenerative Medicine, Bethesda, MD, 20814, USA., De Gasperi R; Research and Development Service, James J. Peters Department of Veterans Affairs Medical Center, 130 West Kingsbridge Road, Bronx, NY, 10468, USA.; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, NY, 10029, USA., Gama Sosa MA; Research and Development Service, James J. Peters Department of Veterans Affairs Medical Center, 130 West Kingsbridge Road, Bronx, NY, 10468, USA.; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, NY, 10029, USA., Perez-Garcia G; Research and Development Service, James J. Peters Department of Veterans Affairs Medical Center, 130 West Kingsbridge Road, Bronx, NY, 10468, USA.; Department of Neurology, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, NY, 10029, USA., Short JA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, NY, 10029, USA., Sosa H; Research and Development Service, James J. Peters Department of Veterans Affairs Medical Center, 130 West Kingsbridge Road, Bronx, NY, 10468, USA.; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, NY, 10029, USA., Perez GM; Research and Development Service, James J. Peters Department of Veterans Affairs Medical Center, 130 West Kingsbridge Road, Bronx, NY, 10468, USA., Tschiffely AE; Department of Neurotrauma, Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, MD, 20910, USA., Dams-O'Connor K; Department of Neurology, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, NY, 10029, USA.; Department of Rehabilitation and Physical Medicine, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, NY, 10029, USA., Pullman MY; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, NY, 10029, USA., Knesaurek K; Department of Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA., Knutsen A; Center for Neuroscience and Regenerative Medicine, Bethesda, MD, 20814, USA., Pham DL; Center for Neuroscience and Regenerative Medicine, Bethesda, MD, 20814, USA., Soleimani L; Department of Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA., Jordan BD; Burke Rehabilitation and Research, 785 Mamaroneck Avenue, White Plains, NY, 10605, USA., Gordon WA; Department of Rehabilitation and Physical Medicine, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, NY, 10029, USA., Delman BN; Department of Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA., Shumyatsky G; Department of Genetics, Rutgers University, Piscataway, NJ, 08854, USA., Shahim PP; Center for Neuroscience and Regenerative Medicine, Bethesda, MD, 20814, USA.; National Institute of Neurological Disorders and Stroke, NIH Neurological Institute, PO Box 5081, Bethesda, MD, 20824, USA., DeKosky ST; Department of Neurology, University of Florida, Gainesville, FL, 32611, USA., Stone JR; Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, VI, 2903, USA., Peskind E; VA Northwest Network Mental Illness Research, Education, and Clinical Center, Seattle, WA, 98195, USA.; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, 98195, USA., Blennow K; Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, S-431 80, Mölndal, Sweden.; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, S-431 80, Mölndal, Sweden., Zetterberg H; Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, S-431 80, Mölndal, Sweden.; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, S-431 80, Mölndal, Sweden.; UK Dementia Research Institute at UCL, London, WC1E 6BT, UK.; Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK., Chance SA; Nuffield Department of Clinical Neurosciences, University of Oxford, Neuropathology, West Wing, Level 1, Oxford, OX3 9DU, UK., Torso M; Nuffield Department of Clinical Neurosciences, University of Oxford, Neuropathology, West Wing, Level 1, Oxford, OX3 9DU, UK., Kostakoglu L; Department of Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA., Sano M; Research and Development Service, James J. Peters Department of Veterans Affairs Medical Center, 130 West Kingsbridge Road, Bronx, NY, 10468, USA.; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, NY, 10029, USA.; Mount Sinai Alzheimer's Disease Research Center and Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Hof PR; Mount Sinai Alzheimer's Disease Research Center and Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, One Gustave Levy, New York, NY, 10029, USA.; Department of Geriatrics and Palliative Care, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Ahlers ST; Department of Neurotrauma, Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, MD, 20910, USA., Gandy S; Research and Development Service, James J. Peters Department of Veterans Affairs Medical Center, 130 West Kingsbridge Road, Bronx, NY, 10468, USA. samuel.gandy@mssm.edu.; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, NY, 10029, USA. samuel.gandy@mssm.edu.; Department of Neurology, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, NY, 10029, USA. samuel.gandy@mssm.edu.; Mount Sinai Alzheimer's Disease Research Center and Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. samuel.gandy@mssm.edu.; NFL Neurological Care Center, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. samuel.gandy@mssm.edu.; Neurology Service, James J. Peters Department of Veterans Affairs Medical Center, 130 West Kingsbridge Road, Bronx, NY, 10468, USA. samuel.gandy@mssm.edu.; South Australian Health and Research Medical Institute, Adelaide, 5000, South Australia. samuel.gandy@mssm.edu., Elder GA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, NY, 10029, USA. gregory.elder@va.gov.; Department of Neurology, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, NY, 10029, USA. gregory.elder@va.gov.; Mount Sinai Alzheimer's Disease Research Center and Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. gregory.elder@va.gov.; Neurology Service, James J. Peters Department of Veterans Affairs Medical Center, 130 West Kingsbridge Road, Bronx, NY, 10468, USA. gregory.elder@va.gov.
Jazyk: angličtina
Zdroj: Molecular psychiatry [Mol Psychiatry] 2021 Oct; Vol. 26 (10), pp. 5940-5954. Date of Electronic Publication: 2020 Feb 25.
DOI: 10.1038/s41380-020-0674-z
Abstrakt: Traumatic brain injury (TBI) is a risk factor for the later development of neurodegenerative diseases that may have various underlying pathologies. Chronic traumatic encephalopathy (CTE) in particular is associated with repetitive mild TBI (mTBI) and is characterized pathologically by aggregation of hyperphosphorylated tau into neurofibrillary tangles (NFTs). CTE may be suspected when behavior, cognition, and/or memory deteriorate following repetitive mTBI. Exposure to blast overpressure from improvised explosive devices (IEDs) has been implicated as a potential antecedent for CTE amongst Iraq and Afghanistan Warfighters. In this study, we identified biomarker signatures in rats exposed to repetitive low-level blast that develop chronic anxiety-related traits and in human veterans exposed to IED blasts in theater with behavioral, cognitive, and/or memory complaints. Rats exposed to repetitive low-level blasts accumulated abnormal hyperphosphorylated tau in neuronal perikarya and perivascular astroglial processes. Using positron emission tomography (PET) and the [ 18 F]AV1451 (flortaucipir) tau ligand, we found that five of 10 veterans exhibited excessive retention of [ 18 F]AV1451 at the white/gray matter junction in frontal, parietal, and temporal brain regions, a typical localization of CTE tauopathy. We also observed elevated levels of neurofilament light (NfL) chain protein in the plasma of veterans displaying excess [ 18 F]AV1451 retention. These findings suggest an association linking blast injury, tauopathy, and neuronal injury. Further study is required to determine whether clinical, neuroimaging, and/or fluid biomarker signatures can improve the diagnosis of long-term neuropsychiatric sequelae of mTBI.
(© 2020. The Author(s).)
Databáze: MEDLINE
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