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Astrocytic degeneration in chronic traumatic encephalopathy

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Abstract

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repeated head traumas. Using immunohistochemistry for glial fibrillary acidic protein as a marker, plus automated quantitative analysis, we examined the characteristics and extent of astrogliosis present in stage III and IV CTE, along with Alzheimer’s disease (AD), and frontotemporal dementia (FTD) cases. Astrogliosis in CTE patients was more diffuse compared to that of AD and FTD patients, which was concentrated in the sulcal depths. Of 14 patients with CTE, 10 exhibited signs of a degenerating astrocyte pathology, characterized by beaded, broken astrocytic processes. This astrocytic degeneration was typically found to be diffuse throughout the white matter, although two cases demonstrated astrocytic degeneration in the gray matter. The degeneration was also observed in 2 of 3 AD and 2 of 3 FTD brains, with overall similar characteristics across diseases. There was minimal to no astrocytic degeneration in six age-matched controls with no neurodegenerative disease. We found that the extent of the white matter astrocytic degeneration was strongly correlated with the level of overall astrogliosis in both the white and gray matter. However, astrocytic degeneration was not correlated with the overall extent of tau pathology. Specifically, there was no correlation between levels of p-tau in the sulcal depths and astrocytic degeneration in the white matter adjacent to the sulcal depths. Thus, astrocytic degeneration and overall astrogliosis appear to represent distinct pathological features of CTE. Further investigation into these astroglial pathologies could provide new insights into underlying disease mechanisms and represent a potential target for in vivo assessment of CTE as well as other neurodegenerative disorders.

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Acknowledgements

We would like to thank the donors and their families for the generous brain donation which made this research possible. We would also like to thank VA Boston Healthcare System and Boston University Alzheimer’s Disease and CTE Center for sample procurement. The studies presented in this work were carried out, in part, using the Hope Center Alafi Neuroimaging Lab, Washington University in St. Louis and the Washington University Center for Cellular Imaging (P30 NS057105). We would also like to thank Marc Goldfinger, Steve Gentleman, Dan Perl, Thomas J. Esparza, and Andrew Sauerbeck for helpful discussions. This research was funded by the National Institute of Health, and the views expressed are those of the authors. NIH UO1 NS086659-02 (Overall PI: A. McKee, Subproject 3 PI: Brody), the US Department of Veterans Affairs, the National Operating Committee on Standards for Athletic Equipment, the Concussion Legacy Foundation, the Andlinger Family Foundation, the WWE, and the NFL. Additional support was provided by a SURF fellowship from Washington University to E. Hsu.

Funding

NIH UO1 NS086659-02 (Overall PI: A. McKee, Subproject 3 PI: Brody).

Author information

Author notes

  1. Laurena Holleran

    Present address: Centre for Neuroimaging and Cognitive Genomics, National University of Ireland, Galway, Ireland

  2. David L. Brody

    Present address: Uniformed Services University of the Health Sciences, Bethesda, MD, USA

Authors and Affiliations

  1. Department of Neurology, Washington University, St. Louis, MO, USA

    Eric T. Hsu, Laurena Holleran & David L. Brody

  2. Department of Biomedical Engineering, Washington University, St. Louis, MO, USA

    Mihika Gangolli, Shiran Su & David L. Brody

  3. VA Boston Healthcare System, Boston, MA, USA

    Thor D. Stein, Victor E. Alvarez & Ann C. McKee

  4. Boston University Alzheimer’s Disease and CTE Center, Boston University School of Medicine, Boston, MA, USA

    Thor D. Stein, Victor E. Alvarez & Ann C. McKee

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

    Thor D. Stein, Victor E. Alvarez & Ann C. McKee

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

    Ann C. McKee

  7. Department of Pathology and Immunology, Washington University, St. Louis, Missouri, USA

    Robert E. Schmidt & David L. Brody

  8. Hope Center for Neurological Disorders, Washington University, St. Louis, Missouri, USA

    David L. Brody

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  8. Robert E. Schmidt
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  9. David L. Brody
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Hsu, E.T., Gangolli, M., Su, S. et al. Astrocytic degeneration in chronic traumatic encephalopathy. Acta Neuropathol 136, 955–972 (2018). https://doi.org/10.1007/s00401-018-1902-3

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  • DOI: https://doi.org/10.1007/s00401-018-1902-3

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