{"doi":"10.1093/brain/awaf073","title":"Traumatic brain injury or head impacts from contact sports are associated with tau astrogliopathy","abstract":"Exposure to traumatic brain injury (TBI) and/or repetitive head impacts (RHI) increase the risk of a range of neurodegenerative pathologies, including chronic traumatic encephalopathy neuropathologic change (CTE-NC). Astrocytic tau pathology reminiscent of ageing-related tau astrogliopathy is a component feature of CTE-NC in many cases. Yet the relationship between TBI/RHI exposure and wider tau astrogliopathy, beyond that of CTE-NC, remains poorly characterized. Autopsy-derived material from 556 individuals was selected to include cases with a history of moderate or severe traumatic brain injury (survival >6 months, n = 77) or a history of participation in contact sports (n = 45), for comparison with uninjured controls with (n = 397) or without (n = 37) neuropathologically confirmed neurodegenerative disease. Representative tissue sections from multiple brain regions were then immunostained for hyperphosphorylated tau (p-tau; PHF-1) and assessed in accordance with the harmonized evaluation criteria for ageing-related tau astrogliopathy. PHF-1-immunoreactive thorn-shaped astrocytes were observed more frequently in contact sports participants (75.6%) versus controls with (32.5%; P < 0.001) and without (8.1%; P < 0.001) neurodegenerative disease. In addition, although the prevalence of thorn-shaped astrocytes following moderate/severe TBI (32.5%) was similar to neurodegenerative disease controls, regression analyses demonstrated increased odds of thorn-shaped astrocytes, when adjusting for age and sex (odds ratio 2.42, 95% confidence interval 1.29-4.54). These findings were observed regardless of whether the pathognomonic lesion of CTE-NC was present in the regions examined. Intriguingly, although subpial thorn-shaped astrocytes at sulcal depths were occasionally observed in aged controls with (3.6%) and without (2.8%) neurodegenerative disease, this pathology was considerably more common following RHI/TBI (42.2%; P < 0.001). These findings support a history of RHI or TBI as an independent risk factor for the development of thorn-shaped tau astrogliopathy, over and above ageing-related tau astrogliopathy observed in ageing and wider neurodegenerative disease. Moreover, trauma might be associated with thorn-shaped astrocytes within specific distributions, including the subpial region of the cortical sulcal depths. The clinical significance of these observations will be important to determine.","journal":"Brain","year":2025,"id":519309,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9546,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":306044,"name":"William Stewart","orcid":"0000-0003-2199-2582","position":1,"is_corresponding":false},{"id":227415,"name":"Gábor G. Kovács","orcid":"0000-0003-3841-5511","position":2,"is_corresponding":false},{"id":107087,"name":"Edward B. Lee","orcid":"0000-0002-4589-1180","position":3,"is_corresponding":false},{"id":227427,"name":"John Robinson","orcid":"0000-0001-6858-2367","position":4,"is_corresponding":false},{"id":27604,"name":"Virginia M.‐Y. Lee","orcid":"0000-0003-3536-6902","position":5,"is_corresponding":false},{"id":27606,"name":"John Q. Trojanowski","orcid":"0000-0002-9239-8794","position":6,"is_corresponding":false},{"id":466935,"name":"Andrea L.C. Schneider","orcid":"0000-0003-0026-5052","position":7,"is_corresponding":false},{"id":306043,"name":"Douglas H. Smith","orcid":"0000-0002-0813-421X","position":8,"is_corresponding":false},{"id":306756,"name":"Victoria E Johnson","orcid":null,"position":9,"is_corresponding":false},{"id":306042,"name":"John D. Arena","orcid":"0000-0002-4322-4472","position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":null,"created_at":"2026-07-19T02:49:18.751199Z","pmid":"40171950","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}