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A better understanding of factors that can prevent or delay AD is vital to improve outcomes for adults with DS. In this narrative review, we apply AD and cognitive aging research frameworks to study resistance and resilience in DSAD. Given the variability in the timing of pathology and symptoms, we discuss the evidence supporting the role of genetic, biological, socio\u2010behavioral, lifestyle, and environmental factors in resistance and resilience to DSAD. We also consider how co\u2010occurring health conditions in DS may influence resistance and resilience, and how methods from AD research can be applied to DSAD. Ultimately, this framework aims to guide future research and translate findings into clinical interventions to improve outcomes in DSAD.<\/jats:p><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Definitions of resistance and resilience in the genetic form of Alzheimer's disease (DSAD) are proposed for guiding the field.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Variability in the timing of AD pathology and symptoms suggests the potential for resistance and resilience mechanisms in DSAD.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Genetic, biological, socio\u2010behavioral, lifestyle, and environmental factors have the potential to build resistance or resilience in DSAD.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Future research will require longitudinal and experimental designs, life course approaches, and large cohort studies.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><\/jats:sec>","DOI":"10.1002\/alz.70151","type":"journal-article","created":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T05:20:02Z","timestamp":1745817602000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Resistance and resilience to Alzheimer's disease in Down syndrome"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0787-6892","authenticated-orcid":false,"given":"Rory","family":"Boyle","sequence":"first","affiliation":[{"name":"Penn Frontotemporal Degeneration Center Perelman School of Medicine Richards Medical Laboratories University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4105-4254","authenticated-orcid":false,"given":"Elouise A.","family":"Koops","sequence":"additional","affiliation":[{"name":"Department of Radiology Massachusetts General Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beau","family":"Ances","sequence":"additional","affiliation":[{"name":"Department of Neurology Center for Advanced Medicine Neuroscience Center Washington University in St. Louis  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth J.","family":"Andrews","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7016-7576","authenticated-orcid":false,"given":"Eider M.","family":"Arenaza\u2010Urquijo","sequence":"additional","affiliation":[{"name":"Barcelona Institute for Global Health, Environment and Health Over the Life Course Programme, Climate, Air Pollution, Nature and Urban Health Programme Pompeu Fabra University Carrer de la Merc\u00e8  Rossell\u00f3 Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9958-0951","authenticated-orcid":false,"given":"Alexandre","family":"Bejanin","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, Biomedical Research Institute Sant Pau Universitat Aut\u00f2noma de Barcelona, Hospital de la Santa Creu i Sant Pau, Sant Antoni Maria Claret  Barcelona Spain"},{"name":"Center of Biomedical Investigation Network for Neurodegenerative Diseases  Planta Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5125-8226","authenticated-orcid":false,"given":"Adam M.","family":"Brickman","sequence":"additional","affiliation":[{"name":"Taub Institute for Research on Alzheimer's Disease and the Aging Brain G.H. 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