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RHI is the major risk factor for developing chronic traumatic encephalopathy (CTE), a neurodegenerative tauopathy. Recent consensus criteria defined the pathognomonic lesion in CTE as perivascular, hyperphosphorylated tau (p-tau) in neuronal aggregates. Astroglial p-tau is an inconsistent supporting feature and not in itself diagnostic of CTE. This study quantitated the spatial and cellular distribution of p-tau pathology in postmortem dorsolateral frontal cortex of 150 individuals with CTE, from ages 21 to 80\u2009years old, without comorbid pathology. p-Tau-immunoreactive cells were quantitated in the gray matter sulcus, crest, subpial region, and within pathognomonic CTE lesions. Significantly more neuronal p-tau than astrocytic p-tau was found across all cortical regions (p\u2009&amp;lt;\u20090.0001). Sulcal astrocytic p-tau was primarily (75%, p\u2009&amp;lt;\u20090.0001) localized to subpial regions as thorn-shaped astrocytes, a form of age-related tau astrogliopathy. Neuronal p-tau was significantly associated with age, years of RHI exposure, and CTE severity; astrocytic p-tau pathology was only significantly associated with age. These findings strongly support neuronal degeneration as a driving feature of CTE and will help inform future research and the development of fluid biomarkers for the detection of neuronal degeneration in CTE.<\/jats:p>","DOI":"10.1093\/jnen\/nlac065","type":"journal-article","created":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T05:28:45Z","timestamp":1659072525000},"page":"773-780","source":"Crossref","is-referenced-by-count":43,"title":["Tau Pathology in Chronic Traumatic Encephalopathy is Primarily Neuronal"],"prefix":"10.1093","volume":"81","author":[{"given":"Morgane L M D","family":"Butler","sequence":"first","affiliation":[{"name":"From the Department of Anatomy and Neurobiology, Boston University School of Medicine , Boston, Massachusetts, USA"},{"name":"VA Boston Healthcare System , Jamaica Plain, Massachusetts, USA"},{"name":"Boston University Alzheimer\u2019s Disease and CTE Centers, Boston University School of Medicine , Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin","family":"Dixon","sequence":"additional","affiliation":[{"name":"VA Boston Healthcare System , Jamaica Plain, Massachusetts, USA"},{"name":"Boston University Alzheimer\u2019s Disease and CTE Centers, Boston University School of Medicine , Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thor D","family":"Stein","sequence":"additional","affiliation":[{"name":"VA Boston Healthcare System , Jamaica Plain, Massachusetts, USA"},{"name":"Boston University Alzheimer\u2019s Disease and CTE Centers, Boston University School of Medicine , Boston, Massachusetts, USA"},{"name":"VA Bedford Healthcare System , Bedford, Massachusetts, USA"},{"name":"Department of Pathology and Laboratory Medicine, Boston University School of Medicine , Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor E","family":"Alvarez","sequence":"additional","affiliation":[{"name":"VA Boston Healthcare System , Jamaica Plain, Massachusetts, USA"},{"name":"Boston University Alzheimer\u2019s Disease and CTE Centers, Boston University School of Medicine , Boston, Massachusetts, USA"},{"name":"National Center for PTSD, VA Boston Healthcare System , Boston, Massachusetts, USA"},{"name":"VA Bedford Healthcare System , Bedford, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertrand","family":"Huber","sequence":"additional","affiliation":[{"name":"VA Boston Healthcare System , Jamaica Plain, Massachusetts, USA"},{"name":"Boston University Alzheimer\u2019s Disease and CTE Centers, Boston University School of Medicine , Boston, Massachusetts, USA"},{"name":"National Center for PTSD, VA Boston Healthcare System , Boston, Massachusetts, USA"},{"name":"VA Bedford Healthcare System , Bedford, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael E","family":"Buckland","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, Royal Prince Alfred Hospital , Sydney, NSW, Australia"},{"name":"Brain and Mind Centre, University of Sydney , Camperdown, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann C","family":"McKee","sequence":"additional","affiliation":[{"name":"From the Department of Anatomy and Neurobiology, Boston University School of Medicine , Boston, Massachusetts, USA"},{"name":"VA Boston Healthcare System , Jamaica Plain, Massachusetts, USA"},{"name":"Boston University Alzheimer\u2019s Disease and CTE Centers, Boston University School of Medicine , Boston, Massachusetts, USA"},{"name":"National Center for PTSD, VA Boston Healthcare System , Boston, Massachusetts, USA"},{"name":"VA Bedford Healthcare System , Bedford, Massachusetts, USA"},{"name":"Department of Neurology, Boston University School of Medicine , Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1257-981X","authenticated-orcid":false,"given":"Jonathan D","family":"Cherry","sequence":"additional","affiliation":[{"name":"VA Boston Healthcare System , Jamaica Plain, Massachusetts, USA"},{"name":"Boston University Alzheimer\u2019s Disease and CTE Centers, Boston University School of Medicine , Boston, Massachusetts, USA"},{"name":"Department of Pathology and Laboratory Medicine, Boston University School of Medicine , Boston, Massachusetts, USA"},{"name":"Department of Neurology, Boston University School of Medicine , Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,7,28]]},"reference":[{"key":"2024032523472703200_nlac065-B1","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1093\/brain\/aws307","article-title":"The spectrum of disease in chronic 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