{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:21:48Z","timestamp":1790832108256,"version":"4.1.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"16","license":[{"start":{"date-parts":[[2019,4,25]],"date-time":"2019-04-25T00:00:00Z","timestamp":1556150400000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sch\u00f6rling Foundation\u2014Swedish FTD Initiative"},{"DOI":"10.13039\/100009673","name":"Gun and Bertil Stohne\u2019s Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100009673","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Old Servants Foundation"},{"DOI":"10.13039\/501100003792","name":"Swedish Brain Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003792","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Strategic Research Program in Neuroscience at Karolinska Institutet; Swedish Medical Research Council"},{"name":"Regional Agreement on Medical Training and Clinical Research (ALF) between Stockholm County Council and Karolinska Institutet"},{"name":"Swedish Alzheimer foundation"},{"name":"Center for Innovative Medicine"},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Alzheimer\u2019s disease (AD) is the most common neurodegenerative disease worldwide. Familial cases suggest genetic components; however, monogenetic causes are few, and the vast majority of incidences have unknown cause. Sequencing efforts have focused on germline mutations, but improved technology has opened up for studies on somatic mutations in affected brain tissue samples. Here we use ultra-deep sequencing on brain and blood from early-onset AD (EOAD) and late-onset AD (LOAD) patients and non-AD individuals (n\u2009=\u200916). In total, 2.86\u00a0Mb of genomic regions, previously associated with AD, were targeted included 28 genes and upstream and downstream regulatory regions. Tailored downstream bioinformatics filtering identified 11 somatic single nucleotide variants in the temporal cortex in AD patients and none in the controls. One variant was validated to be present at 0.4% allele frequency in temporal cortex of a LOAD patient. This variant was predicted to affect transcription factor binding sites upstream of the CD55 gene, contributing to AD pathogenesis by affecting the complement system. Our results suggest that future studies targeting larger portions of the genome for somatic mutation analysis are important to obtain an increased understanding for the molecular basis of both EOAD and LOAD.<\/jats:p>","DOI":"10.1093\/hmg\/ddz085","type":"journal-article","created":{"date-parts":[[2019,4,22]],"date-time":"2019-04-22T07:07:51Z","timestamp":1555916871000},"page":"2675-2685","source":"Crossref","is-referenced-by-count":25,"title":["Somatic mutation that affects transcription factor binding upstream of CD55 in the temporal cortex of a late-onset Alzheimer disease patient"],"prefix":"10.1093","volume":"28","author":[{"given":"Hafdis T","family":"Helgadottir","sequence":"first","affiliation":[{"name":"Department of Biosciences and Nutrition, Center for Innovative Medicine, Karolinska Institutet, Huddinge, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e4r","family":"Lundin","sequence":"additional","affiliation":[{"name":"Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emelie","family":"Wall\u00e9n Arzt","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Nutrition, Center for Innovative Medicine, Karolinska Institutet, Huddinge, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Karin","family":"Lindstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division for Neurogeriatrics, Karolinska Institutet, Solna, Sweden"},{"name":"Unit for Hereditary Dementias, Theme Aging, Karolinska University Hospital, Solna, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Graff","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division for Neurogeriatrics, Karolinska Institutet, Solna, Sweden"},{"name":"Unit for Hereditary Dementias, Theme Aging, Karolinska University Hospital, Solna, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Eriksson","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Nutrition, Center for Innovative Medicine, Karolinska Institutet, Huddinge, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,4,24]]},"reference":[{"key":"2019091012094005100_ref1","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1038\/ng.2802","article-title":"Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease","volume":"45","author":"Lambert","year":"2013","journal-title":"Nat. Genet."},{"key":"2019091012094005100_ref2","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1016\/j.ajhg.2016.05.014","article-title":"Mosaic loss of chromosome Y in blood is associated with Alzheimer disease","volume":"98","author":"Dumanski","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"2019091012094005100_ref3","doi-asserted-by":"crossref","first-page":"4257","DOI":"10.1038\/s41467-018-06331-w","article-title":"High prevalence of focal and multi-focal somatic genetic variants in the human brain","volume":"9","author":"Keogh","year":"2018","journal-title":"Nat. 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Alzheimers Dis."},{"key":"2019091012094005100_ref9","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1093\/hmg\/ddh134","article-title":"Somatic and germline mosaicism in sporadic early-onset Alzheimer's disease","volume":"13","author":"Beck","year":"2004","journal-title":"Hum. Mol. Genet."},{"key":"2019091012094005100_ref10","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1146\/annurev-genet-120417-031501","article-title":"Somatic mutagenesis in mammals and its implications for human disease and aging","volume":"52","author":"Zhang","year":"2018","journal-title":"Annu. Rev. Genet."},{"key":"2019091012094005100_ref11","doi-asserted-by":"crossref","first-page":"e1006245","DOI":"10.1371\/journal.pgen.1006245","article-title":"The contribution of mosaic variants to autism spectrum disorder","volume":"12","author":"Freed","year":"2016","journal-title":"PLoS Genet."},{"key":"2019091012094005100_ref12","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1101\/gr.162131.113","article-title":"Somatic mutations found in the healthy blood compartment of a 115-yr-old woman demonstrate oligoclonal hematopoiesis","volume":"24","author":"Holstege","year":"2014","journal-title":"Genome Res."},{"key":"2019091012094005100_ref13","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1038\/sj.ejhg.5200373","article-title":"Genetic association of the presenilin-1 regulatory region with early-onset Alzheimer's disease in a population-based sample","volume":"7","author":"van Duijn","year":"1999","journal-title":"Eur. J. Hum. Genet."},{"key":"2019091012094005100_ref14","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/1742-2094-7-24","article-title":"Decay accelerating factor (CD55) protects neuronal cells from chemical hypoxia-induced injury","volume":"7","author":"Wang","year":"2010","journal-title":"J. Neuroinflammation"},{"key":"2019091012094005100_ref15","doi-asserted-by":"crossref","first-page":"2353","DOI":"10.4049\/jimmunol.174.4.2353","article-title":"Decay-accelerating factor (CD55) is expressed by neurons in response to chronic but not acute autoimmune central nervous system inflammation associated with complement activation","volume":"174","author":"van Beek","year":"2005","journal-title":"J. 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