{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:59:13Z","timestamp":1792789153946,"version":"4.5.0"},"reference-count":362,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T00:00:00Z","timestamp":1746403200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Russian state-funded project for ICBFM SB RAS","award":["125012300658-9"],"award-info":[{"award-number":["125012300658-9"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Alzheimer\u2019s disease, a complex neurodegenerative disease, is characterized by the pathological aggregation of insoluble amyloid \u03b2 and hyperphosphorylated tau. Multiple models of this disease have been employed to investigate the etiology, pathogenesis, and multifactorial aspects of Alzheimer\u2019s disease and facilitate therapeutic development. Mammals, especially mice, are the most common models for studying the pathogenesis of this disease in vivo. To date, the scientific literature has documented more than 280 mouse models exhibiting diverse aspects of Alzheimer\u2019s disease pathogenesis. Other mammalian species, including rats, pigs, and primates, have also been utilized as models. Selected aspects of Alzheimer\u2019s disease have also been modeled in simpler model organisms, such as Drosophila melanogaster, Caenorhabditis elegans, and Danio rerio. It is possible to model Alzheimer\u2019s disease not only by creating genetically modified animal lines but also by inducing symptoms of this neurodegenerative disease. This review discusses the main methods of creating induced models, with a particular focus on modeling Alzheimer\u2019s disease on cell cultures. Induced pluripotent stem cell (iPSC) technology has facilitated novel investigations into the mechanistic underpinnings of diverse diseases, including Alzheimer\u2019s. Progress in culturing brain tissue allows for more personalized studies on how drugs affect the brain. Recent years have witnessed substantial advancements in intricate cellular system development, including spheroids, three-dimensional scaffolds, and microfluidic cultures. Microfluidic technologies have emerged as cutting-edge tools for studying intercellular interactions, the tissue microenvironment, and the role of the blood\u2013brain barrier (BBB). Modern biology is experiencing a significant paradigm shift towards utilizing big data and omics technologies. Computational modeling represents a powerful methodology for researching a wide array of human diseases, including Alzheimer\u2019s. Bioinformatic methodologies facilitate the analysis of extensive datasets generated via high-throughput experimentation. It is imperative to underscore the significance of integrating diverse modeling techniques in elucidating pathogenic mechanisms in their entirety.<\/jats:p>","DOI":"10.3390\/brainsci15050486","type":"journal-article","created":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T21:42:09Z","timestamp":1746481329000},"page":"486","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Modeling Alzheimer\u2019s Disease: A Review of Gene-Modified and Induced Animal Models, Complex Cell Culture Models, and Computational Modeling"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1270-7164","authenticated-orcid":false,"given":"Anna M.","family":"Timofeeva","sequence":"first","affiliation":[{"name":"SB RAS Institute of Chemical Biology and Fundamental Medicine, Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6972-9068","authenticated-orcid":false,"given":"Kseniya S.","family":"Aulova","sequence":"additional","affiliation":[{"name":"SB RAS Institute of Chemical Biology and Fundamental Medicine, Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4988-8923","authenticated-orcid":false,"given":"Georgy A.","family":"Nevinsky","sequence":"additional","affiliation":[{"name":"SB RAS Institute of Chemical Biology and Fundamental Medicine, Novosibirsk 630090, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1097\/NEN.0b013e31825018f7","article-title":"Correlation of Alzheimer Disease Neuropathologic Changes with Cognitive Status: A Review of the Literature","volume":"71","author":"Nelson","year":"2012","journal-title":"J. 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