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Consequences of chromosome 21 trisomy include developmental delays, congenital cardiac abnormalities, skeletal abnormalities, and age-related dementia of the Alzheimer\u2019s disease (AD) type. Up to 90% of individuals with DS develop dementia symptoms in their 40s or 50s. Because the biological mechanisms involved in DS-related developmental and age-related pathology are less known, animal models consisting of both lower-order and higher-order animals have been developed. We here review the most pertinent and well-studied DS animal models including models developed in C. elegans, Drosophila, zebrafish, and mice. Molecular pathways involved in DS morbidity that were discovered in animal models will also be discussed.<\/jats:p>","DOI":"10.3390\/ijms26168092","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T07:41:45Z","timestamp":1755848505000},"page":"8092","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Vertebrate and Invertebrate Animal Models for the Study of Down Syndrome"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9685-7599","authenticated-orcid":false,"given":"Ann-Charlotte","family":"Granholm","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41572-019-0143-7","article-title":"Down syndrome","volume":"6","author":"Antonarakis","year":"2020","journal-title":"Nat. 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