{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T03:21:37Z","timestamp":1792898497417,"version":"4.5.0"},"reference-count":78,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T00:00:00Z","timestamp":1712102400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006692","name":"University of Turin","doi-asserted-by":"publisher","award":["LEOG_RILO_22_01"],"award-info":[{"award-number":["LEOG_RILO_22_01"]}],"id":[{"id":"10.13039\/501100006692","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006692","name":"University of Turin","doi-asserted-by":"publisher","award":["GAMP_RILO_22_01"],"award-info":[{"award-number":["GAMP_RILO_22_01"]}],"id":[{"id":"10.13039\/501100006692","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006692","name":"University of Turin","doi-asserted-by":"publisher","award":["2019-ATE-0481"],"award-info":[{"award-number":["2019-ATE-0481"]}],"id":[{"id":"10.13039\/501100006692","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002954","name":"University of Milano-Bicocca","doi-asserted-by":"publisher","award":["LEOG_RILO_22_01"],"award-info":[{"award-number":["LEOG_RILO_22_01"]}],"id":[{"id":"10.13039\/501100002954","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002954","name":"University of Milano-Bicocca","doi-asserted-by":"publisher","award":["GAMP_RILO_22_01"],"award-info":[{"award-number":["GAMP_RILO_22_01"]}],"id":[{"id":"10.13039\/501100002954","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002954","name":"University of Milano-Bicocca","doi-asserted-by":"publisher","award":["2019-ATE-0481"],"award-info":[{"award-number":["2019-ATE-0481"]}],"id":[{"id":"10.13039\/501100002954","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Down syndrome (DS) is a complex chromosomal disorder considered as a genetically determined form of Alzheimer\u2019s disease (AD). Maintenance of brain cholesterol homeostasis is essential for brain functioning and development, and its dysregulation is associated with AD neuroinflammation and oxidative damage. Brain cholesterol imbalances also likely occur in DS, concurring with the precocious AD-like neurodegeneration. In this pilot study, we analyzed, in the brain of the Ts2Cje (Ts2) mouse model of DS, the expression of genes encoding key enzymes involved in cholesterol metabolism and of the levels of cholesterol and its main precursors and products of its metabolism (i.e., oxysterols). The results showed, in Ts2 mice compared to euploid mice, the downregulation of the transcription of the genes encoding the enzymes 3-hydroxy-3-methylglutaryl-CoA reductase and 24-dehydrocholesterol reductase, the latter originally recognized as an indicator of AD, and the consequent reduction in total cholesterol levels. Moreover, the expression of genes encoding enzymes responsible for brain cholesterol oxidation and the amounts of the resulting oxysterols were modified in Ts2 mouse brains, and the levels of cholesterol autoxidation products were increased, suggesting an exacerbation of cerebral oxidative stress. We also observed an enhanced inflammatory response in Ts2 mice, underlined by the upregulation of the transcription of the genes encoding for \u03b1-interferon and interleukin-6, two cytokines whose synthesis is increased in the brains of AD patients. Overall, these results suggest that DS and AD brains share cholesterol cycle derangements and altered oxysterol levels, which may contribute to the oxidative and inflammatory events involved in both diseases.<\/jats:p>","DOI":"10.3390\/antiox13040435","type":"journal-article","created":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T03:37:21Z","timestamp":1712115441000},"page":"435","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Altered Brain Cholesterol Machinery in a Down Syndrome Mouse Model: A Possible Common Feature with Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5035-7401","authenticated-orcid":false,"given":"Erica","family":"Staurenghi","sequence":"first","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Turin, San Luigi Hospital, 10043 Orbassano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2835-2804","authenticated-orcid":false,"given":"Gabriella","family":"Testa","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Turin, San Luigi Hospital, 10043 Orbassano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8954-0366","authenticated-orcid":false,"given":"Valerio","family":"Leoni","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pathology, Hospital Pio XI of Desio, ASST-Brianza and Department of Medicine and Surgery, University of Milano-Bicocca, 20832 Desio, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Cecci","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Turin, San Luigi Hospital, 10043 Orbassano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucrezia","family":"Floro","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Turin, San Luigi Hospital, 10043 Orbassano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8364-9301","authenticated-orcid":false,"given":"Serena","family":"Giannelli","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Turin, San Luigi Hospital, 10043 Orbassano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7028-4251","authenticated-orcid":false,"given":"Eugenio","family":"Barone","sequence":"additional","affiliation":[{"name":"Department of Biochemical Sciences \u201cA. Rossi-Fanelli\u201d, Sapienza University, 00185 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marzia","family":"Perluigi","sequence":"additional","affiliation":[{"name":"Department of Biochemical Sciences \u201cA. Rossi-Fanelli\u201d, Sapienza University, 00185 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3422-821X","authenticated-orcid":false,"given":"Gabriella","family":"Leonarduzzi","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Turin, San Luigi Hospital, 10043 Orbassano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Sottero","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Turin, San Luigi Hospital, 10043 Orbassano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2715-5435","authenticated-orcid":false,"given":"Paola","family":"Gamba","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Turin, San Luigi Hospital, 10043 Orbassano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1202208","DOI":"10.3389\/fnins.2023.1202208","article-title":"Modeling Alzheimer\u2019s disease related phenotypes in the Ts65Dn mouse: Impact of age on Abeta, Tau, pTau, NfL, and behavior","volume":"17","author":"Overk","year":"2023","journal-title":"Front. 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