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Chronic traumatic encephalopathy (CTE) is caused by repetitive head impacts (RHI) and is characterized by sulcal tau pathology. However, quantitative assessments of regional neurodegeneration in CTE have not been described. In this study, we quantified three key neurodegenerative measures, including cortical thickness, neuronal density, and synaptic proteins, in contact sport athletes (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009185) and non-athlete controls (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200952) within the sulcal depth, middle, and gyral crest of the dorsolateral frontal cortex. Cortical thickness and neuronal density were decreased within the sulcus in CTE compared to controls (\n                    <jats:italic>p<\/jats:italic>\n                    \u2019s\u2009&lt;\u20090.05). Measurements of synaptic proteins within the gyral crest showed a reduction of \u03b1-synuclein with CTE stage (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.002) and variable changes in PSD-95 density. After adjusting for age, multiple linear regression models demonstrated a strong association between the duration of contact sports play and cortical thinning (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.001) and neuronal loss (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.032) within the sulcus. Additional regression models, adjusted for tau pathology, suggest that within the sulcus, the duration of play was associated with neuronal loss predominantly through tau pathology. In contrast, the association of duration of play with cortical thinning was minimally impacted by tau pathology. Overall, CTE is associated with cortical atrophy and a predominant sulcal neurodegeneration. Furthermore, the duration of contact sports play is associated with measures of neurodegeneration that are more severe in the cortical sulcus and may occur through tau-dependent and independent mechanisms.\n                  <\/jats:p>","DOI":"10.1007\/s00401-024-02833-8","type":"journal-article","created":{"date-parts":[[2024,12,6]],"date-time":"2024-12-06T14:10:34Z","timestamp":1733494234000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Neurodegeneration in the cortical sulcus is a feature of chronic traumatic encephalopathy and associated with repetitive head impacts"],"prefix":"10.1007","volume":"148","author":[{"given":"Raymond","family":"Nicks","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arsal","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spiro Anthony","family":"Stathas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Kirsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah M.","family":"Horowitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Saltiel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha M.","family":"Calderazzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgane L. 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He reports being principal investigator and co-investigator on clinical trials, and has a patent pending regarding the diagnosis of AD using machine learning. JDC received grant support from the Department of Veterans Affairs Career Development Award and National Institute of Aging Boston University AD Center. YT reports receiving grant support to the Boston University School of Public Health. ACM reports grant support for other works from the NINDS\/NIA, NIA, and VA, and honoraria from the University of Massachusetts, Montefiore Medical Center, Korean Dementia Society, and Texas Neurological Society. The remaining authors report no relevant conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"79"}}