Author:
Dickstein Dara L.,De Gasperi Rita,Gama Sosa Miguel A.,Perez-Garcia Georgina,Short Jennifer A.,Sosa Heidi,Perez Gissel M.,Tschiffely Anna E.,Dams-O’Connor Kristen,Pullman Mariel Y.,Knesaurek Karin,Knutsen Andrew,Pham Dzung L.,Soleimani Lale,Jordan Barry D.,Gordon Wayne A.,Delman Bradley N.,Shumyatsky Gleb,Shahim Pashtun-Poh,DeKosky Steven T.,Stone James R.,Peskind Elaine,Blennow Kaj,Zetterberg Henrik,Chance Steven A.,Torso Mario,Kostakoglu Lale,Sano Mary,Hof Patrick R.,Ahlers Stephen T.,Gandy Sam,Elder Gregory A.
Abstract
AbstractTraumatic 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.
Funder
VHA Office of Research and Development | Rehabilitation Research and Development Service
Alzheimer's Drug Discovery Foundation
U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke
Vetenskapsrådet
U.S. Department of Health & Human Services | NIH | National Institute on Aging
Publisher
Springer Science and Business Media LLC
Subject
Cellular and Molecular Neuroscience,Psychiatry and Mental health,Molecular Biology