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Clustering of tau-immunoreactive pathology in chronic traumatic encephalopathy

Abstract

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disorder which may result from repetitive brain injury. A variety of tau-immunoreactive pathologies are present, including neurofibrillary tangles (NFT), neuropil threads (NT), dot-like grains (DLG), astrocytic tangles (AT), and occasional neuritic plaques (NP). In tauopathies, cellular inclusions in the cortex are clustered within specific laminae, the clusters being regularly distributed parallel to the pia mater. To determine whether a similar spatial pattern is present in CTE, clustering of the tau-immunoreactive pathology was studied in the cortex, hippocampus, and dentate gyrus in 11 cases of CTE and 7 cases of Alzheimer’s disease neuropathologic change (ADNC) without CTE. In CTE: (1) all aspects of tau-immunoreactive pathology were clustered and the clusters were frequently regularly distributed parallel to the tissue boundary, (2) clustering was similar in two CTE cases with minimal co-pathology compared with cases with associated ADNC or TDP-43 proteinopathy, (3) in a proportion of cortical gyri, estimated cluster size was similar to that of cell columns of the cortico-cortical pathways, and (4) clusters of the tau-immunoreactive pathology were infrequently spatially correlated with blood vessels. The NFT and NP in ADNC without CTE were less frequently randomly or uniformly distributed and more frequently in defined clusters than in CTE. Hence, the spatial pattern of the tau-immunoreactive pathology observed in CTE is typical of the tauopathies but with some distinct differences compared to ADNC alone. The spread of pathogenic tau along anatomical pathways could be a factor in the pathogenesis of the disease.

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Acknowledgments

The authors gratefully acknowledge the use of the resources and facilities at the Edith Nourse Rogers Memorial Veterans Hospital (Bedford, MA, USA). We also gratefully acknowledge the help of all members of the Chronic Traumatic Encephalopathy Program at Boston University School of Medicine, VA Boston, and the Bedford VA, as well as the individuals and families whose participation and contributions made this work possible. This work was supported by the National Institute of Neurological Disorders and Stroke (1U01NS086659-01), Department of Veterans Affairs, the Veterans Affairs Biorepository (CSP 501), the Translational Research Center for Traumatic Brain Injury and Stress Disorders (TRACTS), Veterans Affairs Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence (B6796-C), the National Institute of Aging Boston University Alzheimer’s Disease Center (P30AG13846; supplement 0572063345–5). This work was supported by the Charles F. and Joanne Knight Alzheimer’s Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA (P50 AG05681 and P01 AG03991 from the National Institute on Aging). This work was also supported by unrestricted gifts from the National Football League, Andlinger Foundation, and WWE.

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Correspondence to Richard A. Armstrong.

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Informed consent was given for the removal of all brain tissue subject to local ethical committee approval and the 1996 Declaration of Helsinki (as modified Edinburgh 2000).

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Other than the stated grants, the authors report no conflicts of interest.

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Armstrong, R.A., McKee, A.C., Alvarez, V.E. et al. Clustering of tau-immunoreactive pathology in chronic traumatic encephalopathy. J Neural Transm 124, 185–192 (2017). https://doi.org/10.1007/s00702-016-1635-1

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  • DOI: https://doi.org/10.1007/s00702-016-1635-1

Keywords

  • Chronic traumatic encephalopathy (CTE)
  • Alzheimer’s disease neuropathologic change (ADNC)
  • Tauopathy
  • Neurofibrillary tangle
  • Spatial pattern
  • Spatial correlation