{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T16:04:20Z","timestamp":1778774660148,"version":"3.51.4"},"reference-count":290,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T00:00:00Z","timestamp":1749513600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT, Lisbon, Portugal)","doi-asserted-by":"publisher","award":["UIDB\/00276\/2020"],"award-info":[{"award-number":["UIDB\/00276\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT, Lisbon, Portugal)","doi-asserted-by":"publisher","award":["LA\/P\/0059\/2020"],"award-info":[{"award-number":["LA\/P\/0059\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT, Lisbon, Portugal)","doi-asserted-by":"publisher","award":["FCT.2022.08133.PTDC"],"award-info":[{"award-number":["FCT.2022.08133.PTDC"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"FCT Stimulus of the Scientific Employment Program","award":["UIDB\/00276\/2020"],"award-info":[{"award-number":["UIDB\/00276\/2020"]}]},{"name":"FCT Stimulus of the Scientific Employment Program","award":["LA\/P\/0059\/2020"],"award-info":[{"award-number":["LA\/P\/0059\/2020"]}]},{"name":"FCT Stimulus of the Scientific Employment Program","award":["FCT.2022.08133.PTDC"],"award-info":[{"award-number":["FCT.2022.08133.PTDC"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a leading cause of dementia and a growing public health concern worldwide. Despite decades of research, effective disease-modifying treatments remain elusive, partly due to limitations in current experimental models. The purpose of this review is to critically assess and compare existing murine and alternative models of AD to identify key strengths, limitations, and future directions for model development that can enhance translational relevance and therapeutic discovery. Traditional transgenic mouse models have advanced the understanding of amyloid-beta and tau pathologies, but often fail to capture the complexity of sporadic, late-onset AD. In response, alternative models\u2014including zebrafish, Drosophila melanogaster, Caenorhabditis elegans, non-human primates, and human brain organoids\u2014are gaining traction due to their complementary insights and diverse experimental advantages. This review also discusses innovations in genetic engineering, neuroimaging, computational modelling, and drug repurposing that are reshaping the landscape of AD research. By integrating these diverse approaches, the review advocates for a multi-model, multidisciplinary strategy to improve the predictive power, accelerate clinical translation, and inform personalised therapeutic interventions. Ethical considerations and equitable access to diagnostics and emerging treatments are also emphasised. Ultimately, this work aims to support the development of more accurate, effective, and human-relevant models to combat AD.<\/jats:p>","DOI":"10.3390\/ijms26125541","type":"journal-article","created":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T08:18:43Z","timestamp":1749543523000},"page":"5541","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Beyond Transgenic Mice: Emerging Models and Translational Strategies in Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6755-4572","authenticated-orcid":false,"given":"Paula","family":"Alexandra Lopes","sequence":"first","affiliation":[{"name":"CIISA\u2014Centro de Investiga\u00e7\u00e3o Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterin\u00e1ria, Universidade de Lisboa, 1300-477 Lisboa, Portugal"},{"name":"Laborat\u00f3rio Associado para Ci\u00eancia Animal e Veterin\u00e1ria (AL4AnimalS), Faculdade de Medicina Veterin\u00e1ria, Universidade de Lisboa, 1300-477 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2666-1774","authenticated-orcid":false,"given":"Jos\u00e9 L.","family":"Guil-Guerrero","sequence":"additional","affiliation":[{"name":"Departamento de Tecnolog\u00eda de Alimentos, Universidad de Almer\u00eda, 04120 Almer\u00eda, Spain"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"313","DOI":"10.14283\/jpad.2021.15","article-title":"The epidemiology of Alzheimer\u2019s disease modifiable risk factors and prevention","volume":"8","author":"Zhang","year":"2021","journal-title":"J. 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