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

Journal article
Authors D. L. Dickstein
R. De Gasperi
M. G. A. Sosa
G. Perez-Garcia
J. A. Short
H. Sosa
G. M. Perez
A. E. Tschiffely
K. Dams-O'Connor
M. Y. Pullman
K. Knesaurek
A. Knutsen
D. L. Pham
L. Soleimani
B. D. Jordan
W. A. Gordon
B. N. Delman
G. Shumyatsky
P. P. Shahim
S. T. DeKosky
J. R. Stone
E. Peskind
Kaj Blennow
Henrik Zetterberg
S. A. Chance
M. Torso
L. Kostakoglu
M. Sano
P. R. Hof
S. T. Ahlers
S. Gandy
G. A. Elder
Published in Molecular Psychiatry
Pages 15
ISSN 1359-4184
Publication year 2020
Published at Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Pages 15
Language en
Links dx.doi.org/10.1038/s41380-020-0674-...
Keywords persistent postconcussive symptoms, military service members, pet tracer, f-18-av-1451, disorder-related traits, cognitive impairment, tau, model, expression, dementia, disease, Biochemistry & Molecular Biology, Neurosciences & Neurology, Psychiatry
Subject categories Neurosciences

Abstract

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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