Tau immunophenotypes in chronic traumatic encephalopathy recapitulate those of ageing and Alzheimer's disease.

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  • Additional Information
    • Affiliation:
      Department of Neurosurgery, Penn Center for Brain Injury and Repair, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
      Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA
      Translational Neuropathology Research Laboratory, University of Pennsylvania, Philadelphia, PA 19104, USA
      Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
      Department of Neuropathology, Queen Elizabeth University Hospital, Glasgow G51 4TF, UK
      Institute of Neuroscience and Psychology, University of Glasgow, Glasgow, G12 8QQ, UK
    • Abstract:
      Traumatic brain injury (TBI) is a risk factor for neurodegenerative disease, including chronic traumatic encephalopathy (CTE). Preliminary consensus criteria define the pathognomonic lesion of CTE as patchy tau pathology within neurons and astrocytes at the depths of cortical sulci. However, the specific tau isoform composition and post-translational modifications in CTE remain largely unexplored. Using immunohistochemistry, we performed tau phenotyping of CTE neuropathologies and compared this to a range of tau pathologies, including Alzheimer's disease, primary age-related tauopathy, ageing-related tau astrogliopathy and multiple subtypes of frontotemporal lobar degeneration with tau inclusions. Cases satisfying preliminary consensus diagnostic criteria for CTE neuropathological change (CTE-NC) were identified (athletes, n = 10; long-term survivors of moderate or severe TBI, n = 4) from the Glasgow TBI Archive and Penn Neurodegenerative Disease Brain Bank. In addition, material from a range of autopsy-proven ageing-associated and primary tauopathies in which there was no known history of exposure to TBI was selected as non-injured controls (n = 32). Each case was then stained with a panel of tau antibodies specific for phospho-epitopes (PHF1, CP13, AT100, pS262), microtubule-binding repeat domains (3R, 4R), truncation (Tau-C3) or conformation (GT-7, GT-38) and the extent and distribution of staining assessed. Cell types were confirmed with double immunofluorescent labelling. Results demonstrate that astroglial tau pathology in CTE is composed of 4R-immunoreactive thorn-shaped astrocytes, echoing the morphology and immunophenotype of astrocytes encountered in ageing-related tau astrogliopathy. In contrast, neurofibrillary tangles of CTE contain both 3R and 4R tau, with post-translational modifications and conformations consistent with Alzheimer's disease and primary age-related tauopathy. Our observations establish that the astroglial and neurofibrillary tau pathologies of CTE are phenotypically distinct from each other and recapitulate the tau immunophenotypes encountered in ageing and Alzheimer's disease. As such, the immunohistochemical distinction of CTE neuropathology from other mixed 3R/4R tauopathies of Alzheimer's disease and ageing may rest solely on the pattern and distribution of pathology.
    • Journal Subset:
      Allied Health; Biomedical; Europe; Peer Reviewed; UK & Ireland
    • ISSN:
      0006-8950
    • MEDLINE Info:
      PMID: NLM32390044 NLM UID: 0372537
    • Grant Information:
      P30 AG010124/AG/NIA NIH HHS/United States; R01 NS094003/NS/NINDS NIH HHS/United States; P01 AG017586/AG/NIA NIH HHS/United States; TL1 TR001880/TR/NCATS NIH HHS/United States; R01 NS092398/NS/NINDS NIH HHS/United States; U54 NS115322/NS/NINDS NIH HHS/United States; RF1 AG054991/AG/NIA NIH HHS/United States; P01 AG009215/AG/NIA NIH HHS/United States; R01 NS038104/NS/NINDS NIH HHS/United States; F32 AG053036/AG/NIA NIH HHS/United States
    • Publication Date:
      In Process
    • Publication Date:
      20200601
    • DOI:
      10.1093/brain/awaa071
    • Accession Number:
      143456371
  • Citations
    • ABNT:
      ARENA, J. D. et al. Tau immunophenotypes in chronic traumatic encephalopathy recapitulate those of ageing and Alzheimer’s disease. Brain: A Journal of Neurology, [s. l.], v. 143, n. 5, p. 1572–1587, 2020. DOI 10.1093/brain/awaa071. Disponível em: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=rzh&AN=143456371. Acesso em: 29 set. 2020.
    • AMA:
      Arena JD, Smith DH, Lee EB, et al. Tau immunophenotypes in chronic traumatic encephalopathy recapitulate those of ageing and Alzheimer’s disease. Brain: A Journal of Neurology. 2020;143(5):1572-1587. doi:10.1093/brain/awaa071
    • APA:
      Arena, J. D., Smith, D. H., Lee, E. B., Gibbons, G. S., Irwin, D. J., Robinson, J. L., Lee, V. M.-Y., Trojanowski, J. Q., Stewart, W., & Johnson, V. E. (2020). Tau immunophenotypes in chronic traumatic encephalopathy recapitulate those of ageing and Alzheimer’s disease. Brain: A Journal of Neurology, 143(5), 1572–1587. https://doi.org/10.1093/brain/awaa071
    • Chicago/Turabian: Author-Date:
      Arena, John D, Douglas H Smith, Edward B Lee, Garrett S Gibbons, David J Irwin, John L Robinson, Virginia M -Y Lee, John Q Trojanowski, William Stewart, and Victoria E Johnson. 2020. “Tau Immunophenotypes in Chronic Traumatic Encephalopathy Recapitulate Those of Ageing and Alzheimer’s Disease.” Brain: A Journal of Neurology 143 (5): 1572–87. doi:10.1093/brain/awaa071.
    • Harvard:
      Arena, J. D. et al. (2020) ‘Tau immunophenotypes in chronic traumatic encephalopathy recapitulate those of ageing and Alzheimer’s disease’, Brain: A Journal of Neurology, 143(5), pp. 1572–1587. doi: 10.1093/brain/awaa071.
    • Harvard: Australian:
      Arena, JD, Smith, DH, Lee, EB, Gibbons, GS, Irwin, DJ, Robinson, JL, Lee, VM-Y, Trojanowski, JQ, Stewart, W & Johnson, VE 2020, ‘Tau immunophenotypes in chronic traumatic encephalopathy recapitulate those of ageing and Alzheimer’s disease’, Brain: A Journal of Neurology, vol. 143, no. 5, pp. 1572–1587, viewed 29 September 2020, .
    • MLA:
      Arena, John D., et al. “Tau Immunophenotypes in Chronic Traumatic Encephalopathy Recapitulate Those of Ageing and Alzheimer’s Disease.” Brain: A Journal of Neurology, vol. 143, no. 5, May 2020, pp. 1572–1587. EBSCOhost, doi:10.1093/brain/awaa071.
    • Chicago/Turabian: Humanities:
      Arena, John D, Douglas H Smith, Edward B Lee, Garrett S Gibbons, David J Irwin, John L Robinson, Virginia M -Y Lee, John Q Trojanowski, William Stewart, and Victoria E Johnson. “Tau Immunophenotypes in Chronic Traumatic Encephalopathy Recapitulate Those of Ageing and Alzheimer’s Disease.” Brain: A Journal of Neurology 143, no. 5 (May 2020): 1572–87. doi:10.1093/brain/awaa071.
    • Vancouver/ICMJE:
      Arena JD, Smith DH, Lee EB, Gibbons GS, Irwin DJ, Robinson JL, et al. Tau immunophenotypes in chronic traumatic encephalopathy recapitulate those of ageing and Alzheimer’s disease. Brain: A Journal of Neurology [Internet]. 2020 May [cited 2020 Sep 29];143(5):1572–87. Available from: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=rzh&AN=143456371