TY - JOUR
T1 - Brain and blood biomarkers of tauopathy and neuronal injury in humans and rats with neurobehavioral syndromes following blast exposure
AU - Dickstein, Dara L.
AU - De Gasperi, Rita
AU - Gama Sosa, Miguel A.
AU - Perez-Garcia, Georgina
AU - Short, Jennifer A.
AU - Sosa, Heidi
AU - Perez, Gissel M.
AU - Tschiffely, Anna E.
AU - Dams-O’Connor, Kristen
AU - Pullman, Mariel Y.
AU - Knesaurek, Karin
AU - Knutsen, Andrew
AU - Pham, Dzung L.
AU - Soleimani, Lale
AU - Jordan, Barry D.
AU - Gordon, Wayne A.
AU - Delman, Bradley N.
AU - Shumyatsky, Gleb
AU - Shahim, Pashtun Poh
AU - DeKosky, Steven T.
AU - Stone, James R.
AU - Peskind, Elaine
AU - Blennow, Kaj
AU - Zetterberg, Henrik
AU - Chance, Steven A.
AU - Torso, Mario
AU - Kostakoglu, Lale
AU - Sano, Mary
AU - Hof, Patrick R.
AU - Ahlers, Stephen T.
AU - Gandy, Sam
AU - Elder, Gregory A.
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2021/10
Y1 - 2021/10
N2 - 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 [18F]AV1451 (flortaucipir) tau ligand, we found that five of 10 veterans exhibited excessive retention of [18F]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 [18F]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.
AB - 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 [18F]AV1451 (flortaucipir) tau ligand, we found that five of 10 veterans exhibited excessive retention of [18F]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 [18F]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.
UR - http://www.scopus.com/inward/record.url?scp=85079807897&partnerID=8YFLogxK
U2 - 10.1038/s41380-020-0674-z
DO - 10.1038/s41380-020-0674-z
M3 - Article
C2 - 32094584
AN - SCOPUS:85079807897
SN - 1359-4184
VL - 26
SP - 5940
EP - 5954
JO - Molecular Psychiatry
JF - Molecular Psychiatry
IS - 10
ER -