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The \u03b2-amyloid cascade of AD and neurofibrillary tangles are the basis of the current understanding of AD pathogenesis, driving drug investigation and other discoveries. Up until now, no AD models have entirely validated the \u03b2-amyloid cascade hypothesis. AD models must be capable of recapitulating the critical events of this pathology, including \u03b2-amyloid plaques and neurofibrillary tangles. The development of plaques is probably derived from the amyloid precursor protein (APP) and presenilin 1 (PS1) familial Alzheimer\u2019s disease (FAD) mutations, while the tangle-like pathology is determined by tau mutations. Transgenic mouse models struggle to replicate the entire spectrum of AD, particularly neuronal death stemming from \u03b2-amyloid and tau pathologies. Furthermore, the success of these transgenic mice often relies on the overexpression of APP transgenes enclosing FAD-associated mutations at levels beyond physiological. Ultimate species-specific discrepancies in genome and protein composition between the human and the mouse may hinder the accurate recapitulation of AD pathological events in mouse models. Although none of the AD models fully mirrors human pathology, these experimental in vivo animal models have provided valuable insights into \u03b2-amyloid toxicity and the overall pathophysiological basis of AD. Therefore, these experimental models have been widely used in the preclinical evaluation of therapeutic strategies and have played a pivotal role in the development of immunotherapies for AD. In this review, we sum up the main transgenic mouse models used for AD research, whether they are APP mutation-based mice, APP plus presenilin mutation-based mice, or tau mutation-based mice. The specific characteristics of each mouse model and the significance of their use for AD research, focusing on their current advantages and disadvantages, as well as on the progress made and the forthcoming challenges in replicating this neurodegenerative disease, are also highlighted.<\/jats:p>","DOI":"10.3390\/jdad2010002","type":"journal-article","created":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T08:03:05Z","timestamp":1736496185000},"page":"2","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["An Overview of Transgenic Mouse Models for the Study of Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6755-4572","authenticated-orcid":false,"given":"Paula Alexandra","family":"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\/0009-0009-5464-9829","authenticated-orcid":false,"given":"Mafalda Soares","family":"P\u00e1dua","sequence":"additional","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":[[2025,1,10]]},"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 World Health Organization (2023, November 09). 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