{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T22:53:47Z","timestamp":1779231227404,"version":"3.51.4"},"reference-count":37,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T00:00:00Z","timestamp":1737504000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002283","name":"Alzheimer\u2019s Research UK","doi-asserted-by":"publisher","award":["ARUK-SRF2018A-001 and ARUK-SRFEXT2022-001"],"award-info":[{"award-number":["ARUK-SRF2018A-001 and ARUK-SRFEXT2022-001"]}],"id":[{"id":"10.13039\/501100002283","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017510","name":"UK Dementia Research Institute","doi-asserted-by":"publisher","award":["UKDRI-1014"],"award-info":[{"award-number":["UKDRI-1014"]}],"id":[{"id":"10.13039\/501100017510","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Down syndrome, resulting from trisomy of human chromosome 21, is a common form of chromosomal disorder that results in intellectual disability and altered risk of several medical conditions. Individuals with Down syndrome have a greatly increased risk of Alzheimer\u2019s disease (DSAD), due to the presence of the <jats:italic>APP<\/jats:italic> gene on chromosome 21 that encodes the amyloid-\u03b2 precursor protein (APP). APP can be processed to generate amyloid-\u03b2, which accumulates in plaques in the brains of people who have Alzheimer\u2019s disease and is the upstream trigger of disease. Cathepsin B has potential roles in both APP processing and amyloid-\u03b2 degradation and has been suggested to contribute to amyloid-\u03b2 accumulation. An endogenous inhibitor of Cathepsin B, Cystatin B (<jats:italic>CSTB<\/jats:italic>), is encoded on chromosome 21. The abundance of this protein is increased in the brains of individuals with DSAD, which may be associated with a decrease in Cathepsin B activity compared to individuals who have Alzheimer\u2019s disease in the general population. Whether targeting <jats:italic>CSTB<\/jats:italic> can modulate Cathepsin B activity in the context of trisomy of chromosome 21 is unclear. Here we test if reducing CSTB can alter Cathepsin B activity in a mouse and a cellular model of trisomy of chromosome 21. We find that reducing CSTB abundance increases Cathepsin B activity in disomic controls but not in the presence of trisomy of chromosome 21. These findings offer new insights into the role of CSTB in regulating Cathepsin B activity.<\/jats:p>","DOI":"10.1371\/journal.pone.0316822","type":"journal-article","created":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T18:23:18Z","timestamp":1737570198000},"page":"e0316822","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Reduction of Cystatin B results in increased cathepsin B activity in disomic but not Trisomy 21 human cellular and mouse 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