{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:00:43Z","timestamp":1792119643576,"version":"4.4.0"},"reference-count":59,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"6772","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Science"],"published-print":{"date-parts":[[2025,10,30]]},"abstract":"<jats:p>Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease linked to exposure to repetitive head impacts (RHI), yet little is known about its pathogenesis. Applying two single-cell whole-genome sequencing methods to hundreds of neurons from prefrontal cortex of 15 individuals with CTE and 4 with RHI without CTE, we revealed increased somatic single-nucleotide variants in CTE, exhibiting a pattern previously reported in Alzheimer\u2019s disease (AD). Furthermore, we discovered high burdens of somatic small insertions and deletions in a subset of CTE individuals, resembling a known pattern, ID4, also found in AD. Our results suggest that neurons in CTE experience stereotyped mutational processes shared with AD; the absence of similar changes in RHI neurons without CTE suggests that CTE involves mechanisms beyond RHI alone.<\/jats:p>","DOI":"10.1126\/science.adu1351","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T18:01:37Z","timestamp":1761847297000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":14,"title":["Diverse somatic genomic alterations in single neurons in chronic traumatic encephalopathy"],"prefix":"10.1126","volume":"390","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4747-6036","authenticated-orcid":true,"given":"Guanlan","family":"Dong","sequence":"first","affiliation":[{"name":"Division of Genetics and Genomics, Manton Center for Orphan Disease Research, Boston Children\u2019s Hospital, Boston, MA, USA."},{"name":"Department of Pediatrics, Harvard Medical School, Boston, MA, USA."},{"name":"Bioinformatics and Integrative Genomics Program, Harvard Medical School, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5642-0213","authenticated-orcid":true,"given":"Chanthia C.","family":"Ma","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics, Manton Center for Orphan Disease Research, Boston Children\u2019s Hospital, Boston, MA, USA."},{"name":"Department of Pediatrics, Harvard Medical School, Boston, MA, USA."},{"name":"Harvard-MIT MD-PhD Program, Harvard Medical School, Boston, MA, USA."},{"name":"Division of Neuropathology, Department of Pathology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2916-6701","authenticated-orcid":true,"given":"Shulin","family":"Mao","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics, Manton Center for Orphan Disease Research, Boston Children\u2019s Hospital, Boston, MA, USA."},{"name":"Department of Pediatrics, Harvard Medical School, Boston, MA, USA."},{"name":"Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3934-7171","authenticated-orcid":true,"given":"Katherine Sun-Mi","family":"Brown","sequence":"additional","affiliation":[{"name":"Division of Neuropathology, Department of Pathology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0505-4839","authenticated-orcid":true,"given":"Samuel M.","family":"Naik","sequence":"additional","affiliation":[{"name":"Division of Neuropathology, Department of Pathology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8420-9970","authenticated-orcid":true,"given":"Gannon A.","family":"McDonough","sequence":"additional","affiliation":[{"name":"Division of Neuropathology, Department of Pathology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samadhi P.","family":"Wijethunga","sequence":"additional","affiliation":[{"name":"Division of Neuropathology, Department of Pathology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3513-401X","authenticated-orcid":true,"given":"Junho","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Sungkyunkwan University, Suwon, South Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5444-6636","authenticated-orcid":true,"given":"Samantha L.","family":"Kirkham","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics, Manton Center for Orphan Disease Research, Boston Children\u2019s Hospital, Boston, MA, USA."},{"name":"Department of Pediatrics, Harvard Medical School, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2087-4082","authenticated-orcid":true,"given":"Diane D.","family":"Shao","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics, Manton Center for Orphan Disease Research, Boston Children\u2019s Hospital, Boston, MA, USA."},{"name":"Department of Pediatrics, Harvard Medical School, Boston, MA, USA."},{"name":"Department of Neurology, Boston Children\u2019s Hospital, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan D.","family":"Cherry","sequence":"additional","affiliation":[{"name":"Veterans Affairs (VA) Boston Healthcare System, US Department of Veteran Affairs, Boston, MA, USA."},{"name":"Alzheimer\u2019s Disease Research Center and Chronic Traumatic Encephalopathy Center, Chobanian and Avedisian School of Medicine, Boston University, Boston, MA, USA."},{"name":"Department of Pathology and Laboratory Medicine, Chobanian and Avedisian School of Medicine, Boston University, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7604-3619","authenticated-orcid":true,"given":"Madeline","family":"Uretsky","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Disease Research Center and Chronic Traumatic Encephalopathy Center, Chobanian and Avedisian School of Medicine, Boston University, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1219-9827","authenticated-orcid":true,"given":"Elizabeth","family":"Spurlock","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Disease Research Center and Chronic Traumatic Encephalopathy Center, Chobanian and Avedisian School of Medicine, Boston University, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann C.","family":"McKee","sequence":"additional","affiliation":[{"name":"Veterans Affairs (VA) Boston Healthcare System, US Department of Veteran Affairs, Boston, MA, USA."},{"name":"Alzheimer\u2019s Disease Research Center and Chronic Traumatic Encephalopathy Center, Chobanian and Avedisian School of Medicine, Boston University, Boston, MA, USA."},{"name":"Department of Pathology and Laboratory Medicine, Chobanian and Avedisian School of Medicine, Boston University, Boston, MA, USA."},{"name":"Department of Neurology, Chobanian and Avedisian School of Medicine, Boston University, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0416-2854","authenticated-orcid":true,"given":"August Yue","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics, Manton Center for Orphan Disease Research, Boston Children\u2019s Hospital, Boston, MA, USA."},{"name":"Department of Pediatrics, Harvard Medical School, Boston, MA, USA."},{"name":"Broad Institute of MIT and Harvard, Cambridge, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6205-3314","authenticated-orcid":true,"given":"Michael B.","family":"Miller","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics, Manton Center for Orphan Disease Research, Boston Children\u2019s Hospital, Boston, MA, USA."},{"name":"Department of Pediatrics, Harvard Medical School, Boston, MA, USA."},{"name":"Division of Neuropathology, Department of Pathology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA, USA."},{"name":"Broad Institute of MIT and Harvard, Cambridge, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6574-9261","authenticated-orcid":true,"given":"Eunjung Alice","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics, Manton Center for Orphan Disease Research, Boston Children\u2019s Hospital, Boston, MA, USA."},{"name":"Department of Pediatrics, Harvard Medical School, Boston, MA, USA."},{"name":"Broad Institute of MIT and Harvard, Cambridge, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0156-2238","authenticated-orcid":true,"given":"Christopher A.","family":"Walsh","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics, Manton Center for Orphan Disease Research, Boston Children\u2019s Hospital, Boston, MA, USA."},{"name":"Department of Pediatrics, Harvard Medical School, Boston, MA, USA."},{"name":"Broad Institute of MIT and Harvard, Cambridge, MA, USA."},{"name":"Boston Children\u2019s Hospital, Howard Hughes Medical Institute, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-015-1515-z"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12248"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/nlab001"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1080\/02699052.2016.1193631"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182a55f7f"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws307"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1026-5"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03911-7"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12250"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1235122"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07943"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.03.002"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aau3879"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa6806"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1409405"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03477-4"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-022-01180-2"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04640-1"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2013106118"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07532-8"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aao4426"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2024176118"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.02.025"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25611"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-020-02197-9"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2023.2907"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad986"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.246223.118"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2019.12.013"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-018-0539-0"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm6434a2"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.acvd.2014.10.003"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(20)30412-9"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2022.1634"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04403-y"},{"key":"e_1_3_2_37_2","doi-asserted-by":"crossref","unstructured":"Z. Zhou L. J. Luquette G. Dong J. Kim J. Ku K. Kim M. Bae D. D. Shao B. Sahile M. B. Miller A. Y. Huang W. J. Nathan A. Nussenzweig P. J. Park C. Lagier-Tourenne E. A. Lee C. A. Walsh Recurrent patterns of widespread neuronal genomic damage shared by major neurodegenerative disorders. bioRxiv 2025.03.03.641186 [Preprint] (2025); https:\/\/doi.org\/10.1101\/2025.03.03.641186.","DOI":"10.1101\/2025.03.03.641186"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.05.032"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03468-5"},{"key":"e_1_3_2_40_2","doi-asserted-by":"crossref","unstructured":"B. Jin K. S.-M. Brown D. S. Smirnov S. M. Naik S. L. Kirkham E. L. Hennessey G. Dong S. Mao S. P. Wijethunga T. Connors Stewart D. J. Selkoe M. P. Frosch D. H. Oakley B. T. Hyman A. Y. Huang M. B. Miller Neurons accumulate disease-specific somatic genomic changes across tau pathologic states in Alzheimer\u2019s disease. bioRxiv 2025.05.26.656152 [Preprint] (2025); https:\/\/doi.org\/10.1101\/2025.05.26.656152.","DOI":"10.1101\/2025.05.26.656152"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e3181a9d503"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0040-1713620"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2019.00713"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.09.035"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.107524.110"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.07.043"},{"key":"e_1_3_2_48_2","unstructured":"H. Li Aligning sequence reads clone sequences and assembly contigs with BWA-MEM. arXiv:1303.3997 [q-bio.GN] (2013)."},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty191"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2308-7"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v067.i01"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v082.i13"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14049"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.048"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1088\/1742-5468\/2008\/10\/P10008"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1195-2"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq603"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1189"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2010-11-2-r14"},{"key":"e_1_3_2_60_2","unstructured":"G. Dong gldong\/CTE_manuscript_code: v1.0 Zenodo (2025); https:\/\/doi.org\/10.5281\/zenodo.15300743."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.adu1351","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T18:02:18Z","timestamp":1761847338000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.adu1351"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,30]]},"references-count":59,"journal-issue":{"issue":"6772","published-print":{"date-parts":[[2025,10,30]]}},"alternative-id":["10.1126\/science.adu1351"],"URL":"https:\/\/doi.org\/10.1126\/science.adu1351","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2025.03.03.641217","asserted-by":"object"}]},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,30]]},"assertion":[{"value":"2024-10-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadu1351"}}