{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T20:46:20Z","timestamp":1791751580142,"version":"4.3.4"},"reference-count":47,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["#521487152"],"award-info":[{"award-number":["#521487152"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010275","name":"Society of Muscular Diseases","doi-asserted-by":"publisher","award":["Fr2\/1"],"award-info":[{"award-number":["Fr2\/1"]}],"id":[{"id":"10.13039\/501100010275","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Current Opinion in Genetics &amp; Development"],"published-print":{"date-parts":[[2026,12]]},"DOI":"10.1016\/j.gde.2026.102549","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T09:26:23Z","timestamp":1791451583000},"page":"102549","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Update on somatic mutations in major neurodegenerative diseases: mutational signatures in neurons and mosaicism"],"prefix":"10.1016","volume":"101","author":[{"given":"Axel","family":"Freischmidt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen H","family":"Weishaupt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.gde.2026.102549_bib1","article-title":"Amyotrophic lateral sclerosis","volume":"3","author":"Hardiman","year":"2017","journal-title":"Nat Rev Dis Prim"},{"key":"10.1016\/j.gde.2026.102549_bib2","article-title":"Frontotemporal lobar degeneration","volume":"9","author":"Grossman","year":"2023","journal-title":"Nat Rev Dis Prim"},{"key":"10.1016\/j.gde.2026.102549_bib3","article-title":"Parkinson disease","volume":"3","author":"Poewe","year":"2017","journal-title":"Nat Rev Dis Prim"},{"key":"10.1016\/j.gde.2026.102549_bib4","article-title":"Alzheimer disease","volume":"7","author":"Knopman","year":"2021","journal-title":"Nat Rev Dis Prim"},{"key":"10.1016\/j.gde.2026.102549_bib5","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/s41586-025-09096-7","article-title":"The somatic mosaicism across human tissues network","volume":"643","author":"Coorens","year":"2025","journal-title":"Nature"},{"key":"10.1016\/j.gde.2026.102549_bib6","doi-asserted-by":"crossref","DOI":"10.1016\/j.arr.2024.102357","article-title":"Neurodegenerative disorders: mechanisms of degeneration and therapeutic approaches with their clinical relevance","volume":"99","author":"Gadhave","year":"2024","journal-title":"Ageing Res Rev"},{"key":"10.1016\/j.gde.2026.102549_bib7","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.cell.2022.12.032","article-title":"Hallmarks of neurodegenerative diseases","volume":"186","author":"Wilson","year":"2023","journal-title":"Cell"},{"key":"10.1016\/j.gde.2026.102549_bib8","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1038\/s41593-018-0237-7","article-title":"Converging pathways in neurodegeneration, from genetics to mechanisms","volume":"21","author":"Gan","year":"2018","journal-title":"Nat Neurosci"},{"key":"10.1016\/j.gde.2026.102549_bib9","doi-asserted-by":"crossref","first-page":"2748","DOI":"10.1038\/s41380-025-02911-7","article-title":"The genetics of neurodegenerative diseases is the genetics of age-related damage clearance failure","volume":"30","author":"Hardy","year":"2025","journal-title":"Mol Psychiatry"},{"key":"10.1016\/j.gde.2026.102549_bib10","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/j.molmed.2016.07.005","article-title":"Common molecular pathways in amyotrophic lateral sclerosis and frontotemporal dementia","volume":"22","author":"Weishaupt","year":"2016","journal-title":"Trends Mol Med"},{"key":"10.1016\/j.gde.2026.102549_bib11","doi-asserted-by":"crossref","DOI":"10.1016\/j.ebiom.2023.104511","article-title":"The complex genetic architecture of Alzheimer\u2019s disease: novel insights and future directions","volume":"90","author":"Andrews","year":"2023","journal-title":"eBioMedicine"},{"key":"10.1016\/j.gde.2026.102549_bib12","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1093\/bmb\/ldad035","article-title":"Genetics in Parkinson\u2019s disease, state-of-the-art and future perspectives","volume":"149","author":"Trevisan","year":"2024","journal-title":"Br Med Bull"},{"key":"10.1016\/j.gde.2026.102549_bib13","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.pathol.2024.10.006","article-title":"Current concepts and molecular pathology of neurodegenerative diseases","volume":"57","author":"Forrest","year":"2025","journal-title":"Pathology"},{"key":"10.1016\/j.gde.2026.102549_bib14","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/s00401-012-1022-4","article-title":"The genetics and neuropathology of amyotrophic lateral sclerosis","volume":"124","author":"Al-Chalabi","year":"2012","journal-title":"Acta Neuropathol"},{"key":"10.1016\/j.gde.2026.102549_sbref15","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.1016\/j.cell.2024.02.025","article-title":"Contrasting somatic mutation patterns in aging human neurons and oligodendrocytes","volume":"187","author":"Ganz","year":"2024","journal-title":"Cell"},{"key":"10.1016\/j.gde.2026.102549_bib16","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1038\/nature23672","article-title":"A somatic mutation in erythro-myeloid progenitors causes neurodegenerative disease","volume":"549","author":"Mass","year":"2017","journal-title":"Nature"},{"key":"10.1016\/j.gde.2026.102549_bib17","doi-asserted-by":"crossref","first-page":"3719","DOI":"10.1016\/j.cell.2026.03.040","article-title":"Somatic cancer variants enriched in Alzheimer\u2019s disease microglia-like cells drive inflammatory and proliferative states","volume":"189","author":"Huang","year":"2026","journal-title":"Cell"},{"key":"10.1016\/j.gde.2026.102549_bib18","article-title":"Brain somatic mutations observed in Alzheimer\u2019s disease associated with aging and dysregulation of tau phosphorylation","volume":"10","author":"Park","year":"2019","journal-title":"Nat Commun"},{"key":"10.1016\/j.gde.2026.102549_bib19","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1126\/science.aao4426","article-title":"Aging and neurodegeneration are associated with increased mutations in single human neurons","volume":"359","author":"Lodato","year":"2018","journal-title":"Science"},{"key":"10.1016\/j.gde.2026.102549_sbref20","doi-asserted-by":"crossref","DOI":"10.1186\/s13024-025-00895-0","article-title":"Brain somatic mutations in Alzheimer\u2019s disease: linking genetic mosaicism to neurodegeneration","volume":"20","author":"Li","year":"2025","journal-title":"Mol Neurodegener"},{"key":"10.1016\/j.gde.2026.102549_bib21","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1038\/s41586-022-04640-1","article-title":"Somatic genomic changes in single Alzheimer\u2019s disease neurons","volume":"604","author":"Miller","year":"2022","journal-title":"Nature"},{"key":"10.1016\/j.gde.2026.102549_sbref22","article-title":"Neurons accumulate disease-specific somatic genomic changes across tau pathologic states in Alzheimer\u2019s disease","author":"Jin","year":"2025","journal-title":"bioRxiv"},{"key":"10.1016\/j.gde.2026.102549_sbref23","doi-asserted-by":"crossref","first-page":"5766","DOI":"10.1016\/j.cell.2026.06.013","article-title":"Recurrent patterns of TOP1-mediated neuronal genomic damage shared by major neurodegenerative disorders","volume":"189","author":"Zhou","year":"2026","journal-title":"Cell"},{"key":"10.1016\/j.gde.2026.102549_bib24","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.neuron.2011.09.010","article-title":"A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD","volume":"72","author":"Renton","year":"2011","journal-title":"Neuron"},{"key":"10.1016\/j.gde.2026.102549_bib25","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1016\/j.cell.2019.03.001","article-title":"A compendium of mutational signatures of environmental agents","volume":"177","author":"Kucab","year":"2019","journal-title":"Cell"},{"key":"10.1016\/j.gde.2026.102549_bib26","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/s41586-020-1943-3","article-title":"The repertoire of mutational signatures in human cancer","volume":"578","author":"Alexandrov","year":"2020","journal-title":"Nature"},{"key":"10.1016\/j.gde.2026.102549_bib27","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1101\/gr.246223.118","article-title":"Deficiency of nucleotide excision repair is associated with mutational signature observed in cancer","volume":"29","author":"Jager","year":"2019","journal-title":"Genome Res"},{"key":"10.1016\/j.gde.2026.102549_bib28","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-021-25492-9","article-title":"Accelerated functional brain aging in pre-clinical familial Alzheimer\u2019s disease","volume":"12","author":"Gonneaud","year":"2021","journal-title":"Nat Commun"},{"key":"10.1016\/j.gde.2026.102549_bib29","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1046\/j.1471-4159.1999.0720771.x","article-title":"Increased DNA oxidation and decreased levels of repair products in Alzheimer\u2019s disease ventricular CSF","volume":"72","author":"Lovell","year":"1999","journal-title":"J Neurochem"},{"key":"10.1016\/j.gde.2026.102549_bib30","article-title":"RNA sequence analysis of somatic mutations in aging and Parkinson\u2019s disease","author":"Sun","year":"2025","journal-title":"bioRxiv"},{"key":"10.1016\/j.gde.2026.102549_bib31","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2023.113636","article-title":"TDP-43-stratified single-cell proteomics of postmortem human spinal motor neurons reveals protein dynamics in amyotrophic lateral sclerosis","volume":"43","author":"Guise","year":"2024","journal-title":"Cell Rep"},{"key":"10.1016\/j.gde.2026.102549_bib32","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/s41586-022-04403-y","article-title":"Signatures of TOP1 transcription-associated mutagenesis in cancer and germline","volume":"602","author":"Reijns","year":"2022","journal-title":"Nature"},{"key":"10.1016\/j.gde.2026.102549_bib33","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1016\/j.molcel.2012.06.035","article-title":"RNase H2-initiated ribonucleotide excision repair","volume":"47","author":"Sparks","year":"2012","journal-title":"Mol Cell"},{"key":"10.1016\/j.gde.2026.102549_bib34","doi-asserted-by":"crossref","first-page":"14068","DOI":"10.1074\/jbc.M115.653345","article-title":"Topoisomerase I alone is sufficient to produce short DNA deletions and can also reverse nicks at ribonucleotide sites","volume":"290","author":"Huang","year":"2015","journal-title":"J Biol Chem"},{"key":"10.1016\/j.gde.2026.102549_bib35","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.15252\/embj.201490868","article-title":"Error-free and mutagenic processing of topoisomerase 1-provoked damage at genomic ribonucleotides","volume":"34","author":"Sparks","year":"2015","journal-title":"EMBO J"},{"key":"10.1016\/j.gde.2026.102549_bib36","doi-asserted-by":"crossref","first-page":"4696","DOI":"10.1073\/pnas.1818415116","article-title":"Motor neuron disease-associated loss of nuclear TDP-43 is linked to DNA double-strand break repair defects","volume":"116","author":"Mitra","year":"2019","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.gde.2026.102549_bib37","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkaf920","article-title":"RNA\/DNA-binding protein TDP43 regulates DNA mismatch repair genes with implications for genome stability","volume":"53","author":"Provasek","year":"2025","journal-title":"Nucleic Acids Res"},{"key":"10.1016\/j.gde.2026.102549_bib38","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms10805","article-title":"Impact of ribonucleotide incorporation by DNA polymerases \u03b2 and \u03bb on oxidative base excision repair","volume":"7","author":"Crespan","year":"2016","journal-title":"Nat Commun"},{"key":"10.1016\/j.gde.2026.102549_bib39","doi-asserted-by":"crossref","DOI":"10.1016\/j.gde.2026.102514","article-title":"Origins and timing of somatic variants in the brain","volume":"100","author":"Shinagawa","year":"2026","journal-title":"Curr Opin Genet Dev"},{"key":"10.1016\/j.gde.2026.102549_bib40","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1146\/annurev-cellbio-100617-062636","article-title":"Intercellular spread of protein aggregates in neurodegenerative disease","volume":"34","author":"Davis","year":"2018","journal-title":"Annu Rev Cell Dev Biol"},{"key":"10.1016\/j.gde.2026.102549_bib41","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1093\/hmg\/ddh134","article-title":"Somatic and germline mosaicism in sporadic early-onset Alzheimer\u2019s disease","volume":"13","author":"Beck","year":"2004","journal-title":"Hum Mol Genet"},{"key":"10.1016\/j.gde.2026.102549_bib42","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.neurobiolaging.2021.07.010","article-title":"Absence of coding somatic single nucleotide variants within well-known candidate genes in late-onset sporadic Alzheimer\u2019s Disease based on the analysis of multi-omics data","volume":"108","author":"Min","year":"2021","journal-title":"Neurobiol Aging"},{"key":"10.1016\/j.gde.2026.102549_bib43","doi-asserted-by":"crossref","DOI":"10.3389\/fneur.2020.570424","article-title":"Investigation of somatic mutations in human brains targeting genes associated with Parkinson\u2019s disease","volume":"11","author":"Leija-Salazar","year":"2020","journal-title":"Front Neurol"},{"key":"10.1016\/j.gde.2026.102549_sbref44","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1093\/brain\/awaf460","article-title":"Somatic gene mutations in the motor cortex of patients with sporadic amyotrophic lateral sclerosis","volume":"149","author":"Gonz\u00e1lez-Velasco","year":"2026","journal-title":"Brain"},{"key":"10.1016\/j.gde.2026.102549_sbref45","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1038\/s41588-026-02570-6","article-title":"Somatic mosaicism in ALS and FTD identifies focal mutations associated with widespread degeneration","volume":"58","author":"Zhou","year":"2026","journal-title":"Nat Genet"},{"key":"10.1016\/j.gde.2026.102549_bib46","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/j.tins.2026.06.004","article-title":"Targeting DNA mismatch repair in Huntington\u2019s disease","volume":"49","author":"Bunting","year":"2026","journal-title":"Trends Neurosci"},{"key":"10.1016\/j.gde.2026.102549_bib47","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.cell.2024.11.038","article-title":"Long somatic DNA-repeat expansion drives neurodegeneration in Huntington\u2019s disease","volume":"188","author":"Handsaker","year":"2025","journal-title":"Cell"}],"container-title":["Current Opinion in Genetics &amp; Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0959437X26001164?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0959437X26001164?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T20:02:54Z","timestamp":1791748974000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0959437X26001164"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,12]]},"references-count":47,"alternative-id":["S0959437X26001164"],"URL":"https:\/\/doi.org\/10.1016\/j.gde.2026.102549","relation":{},"ISSN":["0959-437X"],"issn-type":[{"value":"0959-437X","type":"print"}],"subject":[],"published":{"date-parts":[[2026,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Update on somatic mutations in major neurodegenerative diseases: mutational signatures in neurons and mosaicism","name":"articletitle","label":"Article Title"},{"value":"Current Opinion in Genetics & Development","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.gde.2026.102549","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Author(s). Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"102549"}}