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Chronic traumatic encephalopathy: neurodegeneration following repetitive concussive and subconcussive brain trauma

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Abstract

Chronic Traumatic Encephalopathy (CTE) is a neurodegenerative disease thought to be caused, at least in part, by repetitive brain trauma, including concussive and subconcussive injuries. It is thought to result in executive dysfunction, memory impairment, depression and suicidality, apathy, poor impulse control, and eventually dementia. Beyond repetitive brain trauma, the risk factors for CTE remain unknown. CTE is neuropathologically characterized by aggregation and accumulation of hyperphosphorylated tau and TDP-43. Recent postmortem findings indicate that CTE may affect a broader population than was initially conceptualized, particularly contact sport athletes and those with a history of military combat. Given the large population that could potentially be affected, CTE may represent an important issue in public health. Although there has been greater public awareness brought to the condition in recent years, there are still many research questions that remain. Thus far, CTE can only be diagnosed post-mortem. Current research efforts are focused on the creation of clinical diagnostic criteria, finding objective biomarkers for CTE, and understanding the additional risk factors and underlying mechanism that causes the disease. This review examines research to date and suggests future directions worthy of exploration.

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Fig. 1
Fig. 2

Abbreviations

Aβ:

Beta amyloid

AD:

Alzheimer’s disease

ALS:

Amyotrophic lateral sclerosis

APOE:

Apolipoprotein E

APP:

Amyloid precursor protein

BOLD:

Blood oxygen level dependent

Cho:

Choline

CSF:

Cerebrospinal fluid

CTE:

Chronic traumatic encephalopathy

CTEM:

Chronic traumatic enceohalomyelopathy

DTI:

Diffusion tensor imaging

ERP:

Event-related potential

fMRI:

Functional magnetic resonance imaging

FDDNP:

2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile

FTD:

Frontotemporal dementia

GT:

Glial tangle

GRN:

Granulin

MAPT:

Microtubule-associated protein tau

MRI:

Magnetic resonance imaging

MRS:

Magnetic Resonance Spectroscopy

NAA:

N-acetyl asparate

NFT:

Neurofibrilary tangle

NT:

Neurophil thread

PCS:

Post-concussion syndrome

PET:

Positron emission tomography

SPECT:

Single photon emission computed tomography

SWI:

Susceptibility weighted imaging

TDP-43:

TAR DNA-binding protein 43

TBI:

Traumatic brain injury

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Acknowledgments

This work was supported by grants from the National Institutes of Health (P30 AG13846; R01 NS078337), as well as a grant from the National Operating Committee on Standards for Athletic Equipment, and an unrestricted gift from the National Football League.

Conflict of interest

No authors on this paper have conflicts of interest to disclose.

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Authors and Affiliations

  1. Center for the Study of Traumatic Encephalopathy, Boston University School of Medicine, 72 East Concord Street, Suite B-7380, Boston, MA, 02118, USA

    Christine M. Baugh, Julie M. Stamm, David O. Riley, Christopher J. Nowinski, Robert C. Cantu, Ann C. McKee & Robert A. Stern

  2. Department of Psychology, University of Colorado at Colorado Springs, Colorado Springs, CO, USA

    Brandon E. Gavett

  3. Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Martha E. Shenton

  4. Center for Clinical Spectroscopy, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Alexander Lin

  5. Sports Legacy Institute, Waltham, MA, USA

    Christopher J. Nowinski & Robert C. Cantu

  6. Department of Neurosurgery, Boston University School of Medicine, Boston, MA, USA

    Robert C. Cantu & Robert A. Stern

  7. Neurosurgery Service, the Department of Surgery, and Sports Medicine, Emerson Hospital, Concord, MA, USA

    Robert C. Cantu

  8. Department of Neurology, Boston University School of Medicine, Boston, MA, USA

    Ann C. McKee & Robert A. Stern

  9. Department of Pathology, Boston University School of Medicine, Boston, MA, USA

    Ann C. McKee

  10. Alzheimer’s Disease Center, Boston University School of Medicine, Boston, MA, USA

    Ann C. McKee & Robert A. Stern

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  1. Christine M. Baugh
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  2. Julie M. Stamm
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  6. Alexander Lin
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  10. Robert A. Stern
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Correspondence to Robert A. Stern.

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Baugh, C.M., Stamm, J.M., Riley, D.O. et al. Chronic traumatic encephalopathy: neurodegeneration following repetitive concussive and subconcussive brain trauma. Brain Imaging and Behavior 6, 244–254 (2012). https://doi.org/10.1007/s11682-012-9164-5

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