Journal
MOLECULAR PSYCHIATRY
Volume 26, Issue 10, Pages 5940-5954Publisher
SPRINGERNATURE
DOI: 10.1038/s41380-020-0674-z
Keywords
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Funding
- Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service Awards [1I01RX000996, I01RX002660, 1I01BX004067, 1I01RX000684, 1I01RX002333, I21RX002069, I21RX002876]
- Alzheimer's Disease Drug Foundation
- NIH [NINDS 5U01NS086625, NICHD K01HD074651-01A]
- NIA [P50AG11508]
- Swedish Research Council [2018-02532]
- European Research Council [681712]
- Swedish State Support for Clinical Research [ALFGBG-720931]
- Werber Family Foundation
- Sara and Gideon Gartner Foundation
- Louis B. Mayer Foundation
- Jennifer and Scott Moskowitz Foundation
- Jane Martin and Stuart Katz Foundation
- Lady Va and Sir Deryck Maughan Foundation
- Georgianne and Dr. Reza Khatib Foundation
- George B. Link Foundation
- Department of Defense [0000B999.0000.000. A1503]
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Traumatic brain injury is a risk factor for neurodegenerative diseases, particularly chronic traumatic encephalopathy. This study identified biomarker signatures associated with chronic anxiety traits and behavioral, cognitive, and memory complaints in individuals exposed to blast injuries.
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 [F-18]AV1451 (flortaucipir) tau ligand, we found that five of 10 veterans exhibited excessive retention of [F-18]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 [F-18]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.
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