{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T14:59:12Z","timestamp":1789743552693,"version":"4.0.1"},"reference-count":42,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["KAKENHI 22H04822"],"award-info":[{"award-number":["KAKENHI 22H04822"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012359","name":"Promotion and Mutual Aid Corporation for Private Schools of Japan","doi-asserted-by":"publisher","award":["Science Research Promotion Fund (2020-2022)"],"award-info":[{"award-number":["Science Research Promotion Fund (2020-2022)"]}],"id":[{"id":"10.13039\/501100012359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004330","name":"Smoking Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004330","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Individuals with Down syndrome (DS), caused by triplication of chromosome 21 (Hsa21), face a significantly increased risk of early-onset Alzheimer's disease (AD) and epilepsy. However, the specific impact of Hsa21 genes on these risks is not yet fully understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate how triplication of mouse chromosome 16 (Mmu16), homologous to Hsa21, affects amyloid-\u03b2 (A\u03b2) accumulation in the brain and epileptic seizures in AD-DS model mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      To generate AD-DS model mice, we crossed a mouse model of aspects of AD\u2014an APPswe\/PS1\n                      <jats:sup>dE9<\/jats:sup>\n                      mouse exhibiting brain A\u03b2 accumulation and sudden death associated with epileptic seizures with DS mouse models carrying an extra copy of partial segments of mouse chromosome 16. We used three DS model lines: Ts1Cje, harboring a triplicated region encoding \u223c70 Hsa21-homologous genes (\n                      <jats:italic toggle=\"yes\">Scaf4<\/jats:italic>\n                      -\n                      <jats:italic toggle=\"yes\">Zbtb21<\/jats:italic>\n                      ); Ts1Rhr with triplication of the\n                      <jats:italic toggle=\"yes\">Cbr3<\/jats:italic>\n                      -\n                      <jats:italic toggle=\"yes\">Fam3b<\/jats:italic>\n                      region; and a newly developed Ts1Kei mouse carrying an extra copy of the\n                      <jats:italic toggle=\"yes\">Scaf4<\/jats:italic>\n                      -\n                      <jats:italic toggle=\"yes\">Cbr1<\/jats:italic>\n                      region. A\u03b2 accumulation was assessed by immunohistochemistry and enzyme-linked immunosorbent assay.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Compared with APPswe\/PS1\n                      <jats:sup>dE9<\/jats:sup>\n                      mice, A\u03b2 deposition and insoluble A\u03b2 levels in the brain decreased in APPswe\/PS1\n                      <jats:sup>dE9<\/jats:sup>\n                      -Ts1Cje mice but not in APPswe\/PS1\n                      <jats:sup>dE9<\/jats:sup>\n                      -Ts1Rhr mice. The high mortality in APPswe\/PS1\n                      <jats:sup>dE9<\/jats:sup>\n                      mice was suppressed by either Ts1Cje- or Ts1Rhr-triplicated region. Despite a tendency for decreased A\u03b2 accumulation in APPswe\/PS1\n                      <jats:sup>dE9<\/jats:sup>\n                      -Ts1Kei mice, the study could not be finished due to the extremely high mortality.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The trisomic region in Ts1Kei mice is suggested to harbor genes associated with decreased A\u03b2 accumulation. Alternatively, the trisomic region in Ts1Rhr mice contains genes suppressing sudden death in APPswe\/PS1\n                      <jats:sup>dE9<\/jats:sup>\n                      mice.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877261469121","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T12:50:33Z","timestamp":1784811033000},"page":"321-335","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Down syndrome-associated trisomic chromosomal regions modify amyloid-\u03b2 accumulation and cause early death in a mouse model of aspects of Alzheimer's disease"],"prefix":"10.1177","volume":"113","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8748-7218","authenticated-orcid":false,"given":"Keiichi","family":"Ishihara","sequence":"first","affiliation":[{"name":"Kyoto Pharmaceutical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruka","family":"Yasui","sequence":"additional","affiliation":[{"name":"Kyoto Pharmaceutical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koki","family":"Harada","sequence":"additional","affiliation":[{"name":"Kyoto Pharmaceutical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Amano","sequence":"additional","affiliation":[{"name":"RIKEN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiko","family":"Saito","sequence":"additional","affiliation":[{"name":"Kyoto Pharmaceutical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kino","family":"Kaneda","sequence":"additional","affiliation":[{"name":"Kyoto Pharmaceutical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mizuki","family":"Katsuda","sequence":"additional","affiliation":[{"name":"Kyoto Pharmaceutical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eri","family":"Kawashita","sequence":"additional","affiliation":[{"name":"Kyoto Pharmaceutical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoka","family":"Hata","sequence":"additional","affiliation":[{"name":"Kyoto Pharmaceutical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reina","family":"Annoura","sequence":"additional","affiliation":[{"name":"Kyoto Pharmaceutical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5582-3341","authenticated-orcid":false,"given":"Kaneyasu","family":"Nishimura","sequence":"additional","affiliation":[{"name":"Kyoto Pharmaceutical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Terasaki","sequence":"additional","affiliation":[{"name":"Kyoto Pharmaceutical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruhiko","family":"Sago","sequence":"additional","affiliation":[{"name":"Sanno Birth Center, Minato-ku, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun","family":"Shimohama","sequence":"additional","affiliation":[{"name":"Sapporo Medical University"},{"name":"Jiseikai Hikarigaoka Hospital, Nerima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Akiba","sequence":"additional","affiliation":[{"name":"Kyoto Pharmaceutical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Yamakawa","sequence":"additional","affiliation":[{"name":"RIKEN"},{"name":"Nagoya City University Graduate School of Medical Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuyuki","family":"Takata","sequence":"additional","affiliation":[{"name":"Kyoto Pharmaceutical University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/jir.12390"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1718"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl203"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy159"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/alz.70294"},{"key":"e_1_3_3_7_2","article-title":"The Down Alzheimer Barcelona Neuroimaging Initiative (DABNI) and its contributions to understanding Alzheimer's disease in Down syndrome: a decade of discovery","volume":"21","author":"Videla L","year":"2025","unstructured":"Videla L, Benejam B, Barroeta I, et al. 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