{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T14:06:35Z","timestamp":1740146795813,"version":"3.37.3"},"reference-count":45,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2022,5,11]],"date-time":"2022-05-11T00:00:00Z","timestamp":1652227200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Alzheimer's Research UK","award":["ARUK-SRF2018A-001"],"award-info":[{"award-number":["ARUK-SRF2018A-001"]}]},{"DOI":"10.13039\/501100017510","name":"UK Dementia Research Institute","doi-asserted-by":"crossref","award":["UKDRI-1014"],"award-info":[{"award-number":["UKDRI-1014"]}],"id":[{"id":"10.13039\/501100017510","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Alzheimer's Society UK","award":["AS-PhD-16-003 2017-20"],"award-info":[{"award-number":["AS-PhD-16-003 2017-20"]}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["098330\/Z\/12\/Z"],"award-info":[{"award-number":["098330\/Z\/12\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council UK","doi-asserted-by":"crossref","award":["MR\/S005145\/1"],"award-info":[{"award-number":["MR\/S005145\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100012317","name":"UCLH Biomedical Research Centre","doi-asserted-by":"publisher","award":["NIHR GOSH BRC award 17DD08"],"award-info":[{"award-number":["NIHR GOSH BRC award 17DD08"]}],"id":[{"id":"10.13039\/501100012317","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Individuals who have Down syndrome (trisomy 21) are at greatly increased risk of developing Alzheimer\u2019s disease, characterised by the accumulation in the brain of amyloid-\u03b2 plaques. Amyloid-\u03b2 is a product of the processing of the amyloid precursor protein, encoded by the <jats:italic>APP<\/jats:italic> gene on chromosome 21. In Down syndrome the first site of amyloid-\u03b2 accumulation is within endosomes, and changes to endosome biology occur early in Alzheimer\u2019s disease. Here, we determine if primary mouse embryonic fibroblasts isolated from a mouse model of Down syndrome can be used to study endosome and APP cell biology. We report that in this cellular model, endosome number, size and APP processing are not altered, likely because <jats:italic>APP<\/jats:italic> is not dosage sensitive in the model, despite three copies of <jats:italic>App<\/jats:italic>.<\/jats:p>","DOI":"10.1371\/journal.pone.0262558","type":"journal-article","created":{"date-parts":[[2022,5,11]],"date-time":"2022-05-11T18:26:40Z","timestamp":1652293600000},"page":"e0262558","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Endosomal structure and APP biology are not altered in a preclinical mouse cellular model of Down syndrome"],"prefix":"10.1371","volume":"17","author":[{"given":"Claudia","family":"Cannavo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen","family":"Cleverley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheryl","family":"Maduro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paige","family":"Mumford","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dale","family":"Moulding","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth M. 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Alzheimer\u2019s dementia in Down syndrome","volume":"35","author":"KY Mok","year":"2014","journal-title":"Neurobiol Aging"},{"key":"pone.0262558.ref035","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/hmg\/ddl437","article-title":"The DYRK1A gene, encoded in chromosome 21 Down syndrome critical region, bridges between \u03b2-amyloid production and tau phosphorylation in Alzheimer disease","volume":"16","author":"R Kimura","year":"2007","journal-title":"Hum Mol Genet"},{"key":"pone.0262558.ref036","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.neurobiolaging.2017.04.018","article-title":"Candidate gene analysis for Alzheimer\u2019s disease in adults with Down syndrome","volume":"56","author":"JH Lee","year":"2017","journal-title":"Neurobiol Aging"},{"key":"pone.0262558.ref037","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1091\/mbc.e11-06-0489","article-title":"Recruitment of OCRL and Inpp5B to phagosomes by Rab5 and APPL1 depletes phosphoinositides and attenuates Akt signaling","volume":"23","author":"M Bohdanowicz","year":"2012","journal-title":"Mol Biol Cell"},{"key":"pone.0262558.ref038","article-title":"Genetic dissection of Down syndrome- associated congenital heart defects using a new mouse mapping panel","author":"E Lana-Elola","year":"2016","journal-title":"Elife"},{"key":"pone.0262558.ref039","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1242\/dmm.029728","article-title":"Rodent models in Down syndrome research: impact and future opportunities.","volume":"10","author":"Y Herault","year":"2017","journal-title":"Dis Model Mech"},{"key":"pone.0262558.ref040","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1073\/pnas.0908953107","article-title":"Alzheimer\u2019s-related endosome dysfunction in Down syndrome is A\u03b2-independent but requires APP and is reversed by BACE-1 inhibition","volume":"107","author":"Y Jiang","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0262558.ref041","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1016\/j.bbalip.2010.05.010","article-title":"Clathrin-dependent APP endocytosis and A\u03b2 secretion are highly sensitive to the level of plasma membrane cholesterol","volume":"1801","author":"J-C Cossec","year":"2010","journal-title":"Biochim Biophys Acta\u2014Mol Cell Biol Lipids"},{"key":"pone.0262558.ref042","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1007\/s007260170001","article-title":"Protein expression in Down syndrome brain","author":"E Engidawork","year":"2001","journal-title":"Amino Acids. Springer"},{"key":"pone.0262558.ref043","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/s00726-007-0618-9","article-title":"Protein expression of BACE1, BACE2 and APP in Down syndrome brains","volume":"35","author":"MS Cheon","year":"2008","journal-title":"Amino Acids"},{"key":"pone.0262558.ref044","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1101\/gr.2090904","article-title":"Gene expression from the aneuploid chromosome in a trisomy mouse model of Down syndrome","volume":"14","author":"R Lyle","year":"2004","journal-title":"Genome Res"},{"key":"pone.0262558.ref045","first-page":"268","article-title":"Dissecting Alzheimer disease in down syndrome using mouse models","author":"XY Choong","year":"2015","journal-title":"Frontiers in Behavioral Neuroscience."}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0262558","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,11]],"date-time":"2022-05-11T18:27:21Z","timestamp":1652293641000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0262558"}},"subtitle":[],"editor":[{"given":"Stephen D.","family":"Ginsberg","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2022,5,11]]},"references-count":45,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5,11]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0262558","relation":{},"ISSN":["1932-6203"],"issn-type":[{"type":"electronic","value":"1932-6203"}],"subject":[],"published":{"date-parts":[[2022,5,11]]}}}