{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T11:42:11Z","timestamp":1778672531144,"version":"3.51.4"},"reference-count":54,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG062500"],"award-info":[{"award-number":["R01AG062500"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007482","name":"Arizona State University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007482","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Alzheimer's disease (AD) is a neurodegenerative disease characterized by amyloid\u2010beta plaques and neurofibrillary tau tangles in the brain, neuroinflammation, and cognitive impairment. The 3xTg\u2010AD mouse is a commonly used model in AD studies. 3xTg\u2010AD males display inconsistent pathology; therefore, most studies utilize females. An understanding of why sexual dimorphism exists in this model is lacking. In humans, low circulating choline levels are associated with elevated AD pathology, while higher choline intake reduces pathology in AD mouse models. Here, we sought to understand if blood choline levels are associated with the sex discrepancies observed in 3xTg\u2010AD mice. Body weight and chow consumption were measured, and blood plasma samples were collected at 3, 6, 9, 12\u2009months of age and at end\u2010point in 3xTg\u2010AD and NonTg mice. 3xTg\u2010AD females and NonTg males consumed more chow and gained more body weight than other groups. Longitudinally, 3xTg\u2010AD mice had lower plasma choline levels than NonTg mice, while levels declined with age in NonTg mice. Female 3xTg\u2010AD mice had higher AD\u2010like pathological burden than males, but males had higher mortality rates across the study. IntelliCage automated phenotyping revealed high water\u2010seeking behavior in males. 3xTg\u2010AD mice displayed higher impulsivity compared to NonTg mice. Males were better at spatial and attention tasks but perseverated during avoidance testing compared with females. These findings demonstrate a persistent reduction in circulating choline levels across the lifespan of 3xTg\u2010AD mice despite adequate dietary intake. Given choline's roles in metabolism, inflammatory regulation, and neuronal function, chronically low circulating choline may contribute to the various dysfunctions observed in this model.<\/jats:p>","DOI":"10.1111\/acel.70330","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T08:02:31Z","timestamp":1766995351000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The\n                    <scp>3xTg<\/scp>\n                    \u2010\n                    <scp>AD<\/scp>\n                    Mouse Model of Alzheimer's Disease Exhibits Lifelong Reductions in Circulating Choline Despite Adequate Dietary Intake, With Sex\u2010Specific Neuropathological and Behavioral Phenotypes"],"prefix":"10.1111","volume":"25","author":[{"given":"Jessica M.","family":"Judd","sequence":"first","affiliation":[{"name":"Arizona State University\u2010Banner Neurodegenerative Disease Research Center at the Biodesign Institute Arizona State University  Tempe Arizona USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Faizan","family":"Mistry","sequence":"additional","affiliation":[{"name":"Arizona State University\u2010Banner Neurodegenerative Disease Research Center at the Biodesign Institute Arizona State University  Tempe Arizona USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wendy","family":"Winslow","sequence":"additional","affiliation":[{"name":"Arizona State University\u2010Banner Neurodegenerative Disease Research Center at the Biodesign Institute Arizona State University  Tempe Arizona USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3683-259X","authenticated-orcid":false,"given":"Savannah","family":"Tallino","sequence":"additional","affiliation":[{"name":"Arizona State University\u2010Banner Neurodegenerative Disease Research Center at the Biodesign Institute Arizona State University  Tempe Arizona USA"},{"name":"School of Life Sciences Arizona State University  Tempe Arizona USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie","family":"Turk","sequence":"additional","affiliation":[{"name":"Arizona State University\u2010Banner Neurodegenerative Disease Research Center at the Biodesign Institute Arizona State University  Tempe Arizona USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2514-6818","authenticated-orcid":false,"given":"Ramon","family":"Velazquez","sequence":"additional","affiliation":[{"name":"Arizona State University\u2010Banner Neurodegenerative Disease Research Center at the Biodesign Institute Arizona State University  Tempe Arizona USA"},{"name":"School of Life Sciences Arizona State University  Tempe Arizona USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,12,29]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"Alzheimer's Association.2025.\u201c2025 Alzheimer's Disease Facts and Figures.\u201dhttps:\/\/www.alz.org\/getmedia\/ef8f48f9\u2010ad36\u201048ea\u201087f9\u2010b74034635c1e\/alzheimers\u2010facts\u2010and\u2010figures.pdf#page=30.12."},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1020884312053"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12040546"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-024-01492-x"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-011-9630-3"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5378.794"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25115803"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.14283\/jpad.2023.30"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2009.02.035"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13775"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010021\u201002323\u20101"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-201014"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu16111767"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/85.5.1275"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064\u2010007\u20109424\u20108"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-5-51"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2025.103578"},{"key":"e_1_2_10_19_1","unstructured":"Institute of Medicine.1998.\u201cA Report of the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and Its Panel on Folate Other B Vitamins and Choline and Subcommittee on Upper Reference Levels of Nutrients. Dietary Reference Intakes for Thiamin Riboflavin Niacin Vitamin B6 Folate Vitamin B12 Pantothenic Acid Biotin and Choline.\u201dhttps:\/\/www.nap.edu\/catalog\/6015.html."},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010023\u201002616\u20107"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1101\/lm.053957.124"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2024.1466415"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-170779"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms251910745"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2013.10.084"},{"key":"e_1_2_10_26_1","article-title":"Automated, Long\u2010Term Behavioral Assay for Cognitive Functions in Multiple Genetic Models of Alzheimer's Disease, Using IntelliCage","volume":"138","author":"Masuda A.","year":"2018","journal-title":"Journal of Visualized Experiments"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nlm.2016.07.001"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.2147\/CLEP.S37929"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2021.01.018"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51296"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nlm.2017.09.002"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0007114512001249"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00434-3"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2004.11.051"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2010-100204"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.crphar.2022.100149"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.07\u20108227com"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13293\u2010023\u201000536\u20105"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974\u2010020\u201001956\u20105"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics12100944"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32205-4"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2010.11.058"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2006.10.029"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu16234167"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2007.04.004"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.14\u2010268482"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13037"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2017.06.003"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0007114515003700"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1080\/07315724.2015.1080127"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201801407"},{"key":"e_1_2_10_52_1","doi-asserted-by":"crossref","unstructured":"Winslow W. 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