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

被引：69

作者：

Dickstein, Dara L. ^{[1
,2
]}

De Gasperi, Rita ^{[3
,4
]}

Gama Sosa, Miguel A. ^{[3
,4
]}

Perez-Garcia, Georgina ^{[3
,5
]}

Short, Jennifer A. ^{[4
]}

Sosa, Heidi ^{[3
,4
]}

Perez, Gissel M. ^{[3
]}

Tschiffely, Anna E. ^{[6
]}

Dams-O'Connor, Kristen ^{[5
,7
]}

Pullman, Mariel Y. ^{[4
]}

Knesaurek, Karin ^{[8
]}

Knutsen, Andrew ^{[2
]}

Pham, Dzung L. ^{[2
]}

Soleimani, Lale ^{[8
]}

Jordan, Barry D. ^{[9
]}

Gordon, Wayne A. ^{[7
]}

Delman, Bradley N. ^{[8
]}

Shumyatsky, Gleb ^{[10
]}

Shahim, Pashtun-Poh ^{[2
,11
]}

DeKosky, Steven T. ^{[12
]}

Stone, James R. ^{[13
]}

Peskind, Elaine ^{[14
,15
]}

Blennow, Kaj ^{[16
,17
]}

Zetterberg, Henrik ^{[16
,17
,18
,19
]}

Chance, Steven A. ^{[20
]}

Torso, Mario ^{[20
]}

Kostakoglu, Lale ^{[8
]}

Sano, Mary ^{[3
,4
,21
,22
]}

Hof, Patrick R. ^{[21
,22
,23
,24
,25
]}

Ahlers, Stephen T. ^{[6
]}

Gandy, Sam ^{[3
,4
,5
,21
,22
,26
,27
,28
]}

Elder, Gregory A. ^{[4
,5
,21
,22
,27
]}

机构：

[1] Uniformed Serv Univ Hlth Sci, Dept Pathol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA

[2] Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA

[3] James J Peters Dept Vet Affairs Med Ctr, Res & Dev Serv, 130 West Kingsbridge Rd, Bronx, NY 10468 USA

[4] Icahn Sch Med Mt Sinai, Dept Psychiat, One Gustave Levy Pl, New York, NY 10029 USA

[5] Icahn Sch Med Mt Sinai, Dept Neurol, One Gustave Levy Pl, New York, NY 10029 USA

[6] Naval Med Res Ctr, Dept Neurotrauma, 503 Robert Grant Ave, Silver Spring, MD 20910 USA

[7] Icahn Sch Med Mt Sinai, Dept Rehabil & Phys Med, One Gustave Levy Pl, New York, NY 10029 USA

[8] Icahn Sch Med Mt Sinai, Dept Mol & Intervent Radiol, One Gustave L Levy Pl, New York, NY 10029 USA

[9] Burke Rehabil & Res, 785 Mamaroneck Ave, White Plains, NY 10605 USA

[10] Rutgers State Univ, Dept Genet, Piscataway, NJ 08854 USA

[11] NINDS, NIH, Neurol Inst, POB 5081, Bethesda, MD 20824 USA

[12] Univ Florida, Dept Neurol, Gainesville, FL 32611 USA

[13] Univ Virginia, Dept Radiol & Med Imaging, Charlottesville, VA USA

[14] VA Northwest Network Mental Illness Res Educ & Cl, Seattle, WA 98195 USA

[15] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA

[16] Univ Gothenburg, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Sahlgrenska Acad, S-43180 Molndal, Sweden

[17] Sahlgrens Univ Hosp, Clin Neurochem Lab, S-43180 Molndal, Sweden

[18] UCL, UK Dementia Res Inst, London WC1E 6BT, England

[19] UCL Inst Neurol, Dept Neurodegenerat Dis, Queen Sq, London WC1N 3BG, England

[20] Univ Oxford, Nuffield Dept Clin Neurosci, Neuropathol, West Wing,Level 1, Oxford OX3 9DU, England

[21] Mt Sinai Alzheimers Dis Res Ctr, New York, NY 10029 USA

[22] Icahn Sch Med Mt Sinai, Ronald M Loeb Ctr Alzheimers Dis, New York, NY 10029 USA

[23] Icahn Sch Med Mt Sinai, Nash Family Dept Neurosci, One Gustave Levy, New York, NY 10029 USA

[24] Icahn Sch Med Mt Sinai, Friedman Brain Inst, One Gustave Levy, New York, NY 10029 USA

[25] Icahn Sch Med Mt Sinai, Dept Geriatr & Palliat Care, New York, NY 10029 USA

[26] Icahn Sch Med Mt Sinai, NFL Neurol Care Ctr, New York, NY 10029 USA

[27] James J Peters Dept Vet Affairs Med Ctr, Neurol Serv, 130 West Kingsbridge Rd, Bronx, NY 10468 USA

[28] South Australian Hlth & Res Med Inst, Adelaide, SA 5000, Australia

来源：

MOLECULAR PSYCHIATRY | 2021年 / 26卷 / 10期

基金：

欧洲研究理事会; 英国医学研究理事会; 瑞典研究理事会;

关键词：

PERSISTENT POSTCONCUSSIVE SYMPTOMS; MILITARY SERVICE MEMBERS; PET TRACER F-18-AV-1451; DISORDER-RELATED TRAITS; COGNITIVE IMPAIRMENT; TAU; MODEL; EXPRESSION; DEMENTIA; DISEASE;

D O I：

10.1038/s41380-020-0674-z

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：5940 / 5954

页数：15

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