{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T23:13:14Z","timestamp":1768345994546,"version":"3.49.0"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T00:00:00Z","timestamp":1730073600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004375","name":"Tel Aviv University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004375","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Anim Models and Exp Med"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Over the past few decades, a threefold increase in obesity and type 2 diabetes (T2D) has placed a heavy burden on the health\u2010care system and society. Previous studies have shown correlations between obesity, T2D, and neurodegenerative diseases, including dementia. It is imperative to further understand the relationship between obesity, T2D, and cognitive deficits.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This investigation tested and evaluated the cognitive impact of obesity and T2D induced by high\u2010fat diet (HFD) and the effect of the host genetic background on the severity of cognitive decline caused by obesity and T2D in collaborative cross (CC) mice. The CC mice are a genetically diverse panel derived from eight inbred strains.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our findings demonstrated significant variations in the recorded phenotypes across different CC lines compared to the reference mouse line, C57BL\/6J. CC037 line exhibited a substantial increase in body weight on HFD, whereas line CC005 exhibited differing responses based on sex. Glucose tolerance tests revealed significant variations, with some lines like CC005 showing a marked increase in area under the curve (AUC) values on HFD. Organ weights, including brain, spleen, liver, and kidney, varied significantly among the lines and sexes in response to HFD. Behavioral tests using the Morris water maze indicated that cognitive performance was differentially affected by diet and genetic background.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study establishes a foundation for future quantitative trait loci mapping using CC lines and identifying genes underlying the comorbidity of Alzheimer's disease (AD), caused by obesity and T2D. The genetic components may offer new tools for early prediction and prevention.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ame2.12488","type":"journal-article","created":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T05:36:18Z","timestamp":1730180178000},"page":"126-141","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The collaborative cross mouse for studying the effect of host genetic background on memory impairments due to obesity and diabetes"],"prefix":"10.1002","volume":"8","author":[{"given":"Avia","family":"Paz","sequence":"first","affiliation":[{"name":"Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine Tel Aviv University  Tel Aviv Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kareem","family":"Midlej","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine Tel Aviv University  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