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Central to our understanding of AD pathogenesis is the \u03b2-amyloid cascade hypothesis, which underlies drug research and discovery efforts. Despite extensive studies, no animal models of AD have completely validated this hypothesis. Effective AD models are essential for accurately replicating key pathological features of the disease, notably the formation of \u03b2-amyloid plaques and neurofibrillary tangles. These pathological markers are primarily driven by mutations in the amyloid precursor protein (APP) and presenilin 1 (PS1) genes in familial AD (FAD) and by tau protein mutations for the tangle pathology. Transgenic mice models have been instrumental in AD research, heavily relying on the overexpression of mutated APP genes to simulate disease conditions. However, these models do not entirely replicate the human condition of AD. This review aims to provide a comprehensive evaluation of the historical and ongoing research efforts in AD, particularly through the use of transgenic mice models. It is focused on the benefits gathered from these transgenic mice models in understanding \u03b2-amyloid toxicity and the broader biological underpinnings of AD. Additionally, the review critically assesses the application of these models in the preclinical testing of new therapeutic interventions, highlighting the gap between animal models and human clinical realities. This analysis underscores the need for refinement in AD research methodologies to bridge this gap and enhance the translational value of preclinical studies.<\/jats:p>","DOI":"10.3390\/ijms25052805","type":"journal-article","created":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T09:26:17Z","timestamp":1709112377000},"page":"2805","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Insights on the Use of Transgenic Mice Models in Alzheimer\u2019s Disease Research"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-5464-9829","authenticated-orcid":false,"given":"Mafalda Soares","family":"P\u00e1dua","sequence":"first","affiliation":[{"name":"CIISA\u2014Centro de Investiga\u00e7\u00e3o Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterin\u00e1ria, Universidade de Lisboa, 1300-477 Lisbon, Portugal"},{"name":"Laborat\u00f3rio Associado para Ci\u00eancia Animal e Veterin\u00e1ria (AL4AnimalS), Faculdade de Medicina Veterin\u00e1ria, Universidade de Lisboa, 1300-477 Lisbon, 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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1032-5987","authenticated-orcid":false,"given":"Jos\u00e9 A. M.","family":"Prates","sequence":"additional","affiliation":[{"name":"CIISA\u2014Centro de Investiga\u00e7\u00e3o Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterin\u00e1ria, Universidade de Lisboa, 1300-477 Lisbon, Portugal"},{"name":"Laborat\u00f3rio Associado para Ci\u00eancia Animal e Veterin\u00e1ria (AL4AnimalS), Faculdade de Medicina Veterin\u00e1ria, Universidade de Lisboa, 1300-477 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6755-4572","authenticated-orcid":false,"given":"Paula Alexandra","family":"Lopes","sequence":"additional","affiliation":[{"name":"CIISA\u2014Centro de Investiga\u00e7\u00e3o Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterin\u00e1ria, Universidade de Lisboa, 1300-477 Lisbon, Portugal"},{"name":"Laborat\u00f3rio Associado para Ci\u00eancia Animal e Veterin\u00e1ria (AL4AnimalS), Faculdade de Medicina Veterin\u00e1ria, Universidade de Lisboa, 1300-477 Lisbon, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.jalz.2012.11.007","article-title":"The global prevalence of dementia: A systematic review and metaanalysis","volume":"9","author":"Prince","year":"2013","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_2","unstructured":"WHO\u2014World Health Organization (2023, November 09). 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