{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T23:25:19Z","timestamp":1789428319215,"version":"build-2803163510"},"reference-count":0,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2014,10,10]],"date-time":"2014-10-10T00:00:00Z","timestamp":1412899200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2014,10,10]]},"abstract":"<jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Although genome-wide association studies have shown that genetic factors increase the risk of suffering late-onset, sporadic Alzheimer\u2019s disease (SAD), the molecular mechanisms responsible remain largely unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>The aim of the study was to investigate the presence of somatic, brain-specific single nucleotide variations (SNV) in the hippocampus of SAD samples.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>By using bioinformatic tools, we compared whole exome sequences in paired blood and hippocampal genomic DNAs from 17 SAD patients and from 2 controls and 2 vascular dementia patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>We found a remarkable number of SNVs in SAD brains (~575 per patient) that were not detected in blood. Loci with hippocampus-specific (hs)-SNVs were common to several patients, with 38 genes being present in 6 or more patients out of the 17. While some of these SNVs were in genes previously related to SAD (e.g., CSMD1, LRP2), most hs-SNVs occurred in loci previously unrelated to SAD. The most frequent genes with hs-SNVs were associated with neurotransmission, DNA metabolism, neuronal transport, and muscular function. Interestingly, 19 recurrent hs-SNVs were common to 3 SAD patients. Repetitive loci or hs-SNVs were underrepresented in the hippocampus of control or vascular dementia donors, or in the cerebellum of SAD patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Our data suggest that adult blood and brain have different DNA genomic variations, and that somatic genetic mosaicism and brain-specific genome reshaping may contribute to SAD pathogenesis and cognitive differences between individuals.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/jad-140891","type":"journal-article","created":{"date-parts":[[2018,6,4]],"date-time":"2018-06-04T06:35:21Z","timestamp":1528094121000},"page":"1357-1382","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":39,"title":["Somatic Signature of Brain-Specific Single Nucleotide Variations in Sporadic Alzheimer's Disease"],"prefix":"10.1177","volume":"42","author":[{"given":"Antoni","family":"Parcerisas","sequence":"first","affiliation":[{"name":"Department of Cell Biology, University of Barcelona, Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, ISCIII), Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara E.","family":"Rubio","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, University of Barcelona, Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, ISCIII), Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashraf","family":"Muhaisen","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, University of Barcelona, Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, ISCIII), Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"G\u00f3mez-Ramos","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, ISCIII), Spain"},{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Llu\u00eds","family":"Pujadas","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, University of Barcelona, Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, ISCIII), Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Montserrat","family":"Puiggros","sequence":"additional","affiliation":[{"name":"Joint IRB-BSC Program in Computational Biology, Barcelona Supercomputing Center, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Rossi","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, University of Barcelona, Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, ISCIII), Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas","family":"Ure\u00f1a","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, University of Barcelona, Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, ISCIII), Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferr\u00e1n","family":"Burgaya","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, University of Barcelona, Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, ISCIII), Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Pascual","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, University of Barcelona, Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, ISCIII), Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Torrents","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, University of Barcelona, Barcelona, Spain"},{"name":"Instituci\u00f3 Catalana de Recerca i Estudis Avan\u00e7ats (ICREA), Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"R\u00e1bano","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n CIEN, Vallecas, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas","family":"\u00c1vila","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, ISCIII), Spain"},{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Soriano","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, University of Barcelona, Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, ISCIII), Spain"},{"name":"Fundaci\u00f3n CIEN, Vallecas, Madrid, Spain"},{"name":"Vall d'Hebr\u00f3n Institut de Recerca (VHIR), Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2014,10,10]]},"container-title":["Journal of Alzheimer\u2019s Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JAD-140891","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JAD-140891","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:00:53Z","timestamp":1777370453000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.3233\/JAD-140891"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,10,10]]},"references-count":0,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2014,10,10]]}},"alternative-id":["10.3233\/JAD-140891"],"URL":"https:\/\/doi.org\/10.3233\/jad-140891","relation":{"is-cited-by":[{"id-type":"doi","id":"10.3389\/fnagi.2016.00138","asserted-by":"object"}]},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,10,10]]}}}