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Despite extensive research efforts employing various methodologies and diverse genetic models focused on amyloid-\u03b2 (A\u03b2) pathology, the research for effective therapeutic strategies remains inconclusive. The key pathological features of AD include A\u03b2 senile plaques, neurofibrillary tangles (NFTs), and the activation of neuroinflammatory pathways. Presently, investigations into AD and assessing potential treatments predominantly utilize A\u03b2 transgenic models. Conversely, non-transgenic models may provide valuable insights into the multifaceted pathological states associated with AD. Thus, these models may serve as practical complementary tools for evaluating therapeutic and intervention strategies, since the primary AD risk factors are most frequently modeled. This review aims to critically assess the existing literature on AD non-transgenic models induced by streptozotocin, scopolamine, aging, mechanical stress, metals, and dietary patterns to enhance their application in AD research.<\/jats:p>","DOI":"10.3390\/brainsci15030322","type":"journal-article","created":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T05:03:59Z","timestamp":1742447039000},"page":"322","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Murine Non-Transgenic Models of Alzheimer\u2019s Disease Pathology: Focus on Risk Factors"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9371-1095","authenticated-orcid":false,"given":"Maricarmen","family":"Hern\u00e1ndez-Rodr\u00edguez","sequence":"first","affiliation":[{"name":"Laboratorio de Cultivo Celular, Neurofarmacolog\u00eda y Conducta, Escuela Superior de Medicina, Instituto Polit\u00e9cnico Nacional, Plan de San Luis y D\u00edaz Mir\u00f3n s\/n, Mexico City 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Manuel","family":"Vega L\u00f3pez","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica In\u00f3rg\u00e1nica, Escuela Nacional de Ciencias Biol\u00f3gicas, Prolongaci\u00f3n de Carpio y Plan de Ayala s\/n, Mexico City 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5687-0345","authenticated-orcid":false,"given":"Mart\u00edn","family":"Mart\u00ednez-Rosas","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez, Juan Badiano 1, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0722-5045","authenticated-orcid":false,"given":"Mar\u00eda In\u00e9s","family":"Nicol\u00e1s-V\u00e1zquez","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias Qu\u00edmicas, Facultad de Estudios Superiores Cuautitl\u00e1n, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Cuautitl\u00e1n Izcalli 54740, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elvia","family":"Mera Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Laboratorio de Cultivo Celular, Neurofarmacolog\u00eda y Conducta, Escuela Superior de Medicina, Instituto Polit\u00e9cnico Nacional, Plan de San Luis y D\u00edaz Mir\u00f3n s\/n, Mexico City 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1111\/jgs.16027","article-title":"Incidence of Dementia and Alzheimer Disease Over Time: A Meta-Analysis","volume":"67","author":"Gao","year":"2019","journal-title":"J. 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