{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T21:36:41Z","timestamp":1783719401234,"version":"3.55.0"},"reference-count":145,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T00:00:00Z","timestamp":1634083200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG070153"],"award-info":[{"award-number":["R01AG070153"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R21AG070297"],"award-info":[{"award-number":["R21AG070297"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG061566"],"award-info":[{"award-number":["R01AG061566"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Itkin Family Foundation","award":["000"],"award-info":[{"award-number":["000"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Down syndrome (DS) is a form of accelerated aging, and people with DS are highly prone to aging-related conditions that include vascular and neurological disorders. Due to the overexpression of several genes on Chromosome 21, for example genes encoding amyloid precursor protein (APP), superoxide dismutase (SOD), and some of the interferon receptors, those with DS exhibit significant accumulation of amyloid, phospho-tau, oxidative stress, neuronal loss, and neuroinflammation in the brain as they age. In this review, we will summarize the major strides in this research field that have been made in the last few decades, as well as discuss where we are now, and which research areas are considered essential for the field in the future. We examine the scientific history of DS bridging these milestones in research to current efforts in the field. We extrapolate on comorbidities associated with this phenotype and highlight clinical networks in the USA and Europe pursuing clinical research, concluding with funding efforts and recent recommendations to the NIH regarding DS research.<\/jats:p>","DOI":"10.3390\/jcm10204687","type":"journal-article","created":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T21:36:15Z","timestamp":1634160975000},"page":"4687","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Aging with Down Syndrome\u2014Where Are We Now and Where Are We Going?"],"prefix":"10.3390","volume":"10","author":[{"given":"Melissa J.","family":"Alldred","sequence":"first","affiliation":[{"name":"Nathan Kline Institute, NYU Grossman Medical School, 140 Old Orangeburg Rd, Orangeburg, NY 10962, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra C.","family":"Martini","sequence":"additional","affiliation":[{"name":"Department of Pathology and Lab. Medicine, University of California Irvine, Irvine, CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3530-5686","authenticated-orcid":false,"given":"David","family":"Patterson","sequence":"additional","affiliation":[{"name":"Knoebel Institute for Healthy Aging, University of Denver, Denver, CO 80208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3752-0857","authenticated-orcid":false,"given":"James","family":"Hendrix","sequence":"additional","affiliation":[{"name":"LuMind IDSC Foundation, 20 Mall Road, Suite 200, Burlington, MA 01801, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann-Charlotte","family":"Granholm","sequence":"additional","affiliation":[{"name":"Knoebel Institute for Healthy Aging, University of Denver, Denver, CO 80208, USA"},{"name":"Department of Neurosurgery, CU Anschutz, 12631 East 17th Avenue, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,13]]},"reference":[{"key":"ref_1","first-page":"1721","article-title":"Study of somatic chromosomes from 9 mongoloid children","volume":"248","author":"Lejeune","year":"1959","journal-title":"Comptes Rendus Hebd. 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