{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T16:29:30Z","timestamp":1772209770376,"version":"3.50.1"},"reference-count":45,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T00:00:00Z","timestamp":1626912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical Research Council","award":["MR\/S005145\/1"],"award-info":[{"award-number":["MR\/S005145\/1"]}]},{"name":"Alzheimer\u2019s Research UK Senior Research Fellowship","award":["ARUK-SRF2018A-001"],"award-info":[{"award-number":["ARUK-SRF2018A-001"]}]},{"name":"UK Medical Research Council, Alzheimer\u2019s Society and Alzheimer\u2019s Research UK","award":["UKDRI-1014"],"award-info":[{"award-number":["UKDRI-1014"]}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/S005145\/1"],"award-info":[{"award-number":["MR\/S005145\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"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"}]},{"name":"Wellcome Trust Joint Senior Investigators Award","award":["098328, 098327"],"award-info":[{"award-number":["098328, 098327"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    People with Down syndrome (DS), caused by trisomy of chromosome 21 have a greatly increased risk of developing Alzheimer\u2019s disease (AD). This is in part because of triplication of a chromosome 21 gene,\n                    <jats:italic>APP<\/jats:italic>\n                    . This gene encodes amyloid precursor protein, which is cleaved to form amyloid-\u03b2 that accumulates in the brains of people who have AD. Recent experimental results demonstrate that a gene or genes on chromosome 21, other than\n                    <jats:italic>APP<\/jats:italic>\n                    , when triplicated significantly accelerate amyloid-\u03b2 pathology in a transgenic mouse model of amyloid-\u03b2 deposition. Multiple lines of evidence indicate that cysteine cathepsin activity influences APP cleavage and amyloid-\u03b2 accumulation. Located on human chromosome 21 (Hsa21) is an endogenous inhibitor of cathepsin proteases,\n                    <jats:italic>CYSTATIN B<\/jats:italic>\n                    (\n                    <jats:italic>CSTB)<\/jats:italic>\n                    which is proposed to regulate cysteine cathepsin activity\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Here we determined if three copies of the mouse gene\n                    <jats:italic>Cstb<\/jats:italic>\n                    is sufficient to modulate amyloid-\u03b2 accumulation and cathepsin activity in a transgenic\n                    <jats:italic>APP<\/jats:italic>\n                    mouse model. Duplication of\n                    <jats:italic>Cstb<\/jats:italic>\n                    resulted in an increase in transcriptional and translational levels of\n                    <jats:italic>Cstb<\/jats:italic>\n                    in the mouse cortex but had no effect on the deposition of insoluble amyloid-\u03b2 plaques or the levels of soluble or insoluble amyloid-\u03b242, amyloid-\u03b2\n                    <jats:sub>40<\/jats:sub>\n                    , or amyloid-\u03b2\n                    <jats:sub>38<\/jats:sub>\n                    in 6-month old mice. In addition, the increased CSTB did not alter the activity of cathepsin B enzyme in the cortex of 3-month or 6-month old mice. These results indicate that the single-gene duplication of\n                    <jats:italic>Cstb<\/jats:italic>\n                    is insufficient to elicit a disease-modifying phenotype in the dupCstb x tgAPP mice, underscoring the complexity of the genetic basis of AD-DS and the importance of multiple gene interactions in disease.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0242236","type":"journal-article","created":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T13:50:07Z","timestamp":1626961807000},"page":"e0242236","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["The effects of Cstb duplication on APP\/amyloid-\u03b2 pathology and cathepsin B activity in a mouse model"],"prefix":"10.1371","volume":"16","author":[{"given":"Yixing","family":"Wu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1916-9098","authenticated-orcid":true,"given":"Heather T.","family":"Whittaker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suzanna","family":"Noy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen","family":"Cleverley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veronique","family":"Brault","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7049-6900","authenticated-orcid":true,"given":"Yann","family":"Herault","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth M. 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