{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T02:15:05Z","timestamp":1787624105996,"version":"build-2736575974"},"reference-count":96,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T00:00:00Z","timestamp":1745798400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AG060752"],"award-info":[{"award-number":["AG060752"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Alzheimer\u2019s disease (AD) is characterized by progressive cognitive decline and has a long prodromal phase during which subclinical cognitive deficits and neuropsychiatric symptoms may begin to emerge. Apathy, defined as a lack of motivation or volition, is increasingly recognized as a core feature and a potentially early marker of AD. Despite its significance, apathy-like behavior has been underexplored in transgenic models of AD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a longitudinal analysis of apathy-like behavior using the well-established TgF344-AD rat model. We compared male and female TgF344-AD and wildtype rats on hedonic (palatable food intake) and motivational (progressive ratio) assays during early (3\u20144 months), intermediate (6\u20137 months), and later (9\u201310 months) stages of adulthood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that female TgF344-AD rats exhibited early and persistent deficits in motivational and hedonic feeding, emerging at 3\u20134 months and 6\u20137 months, respectively. During a battery of cognitive tests conducted after 12\u201314 months of age, TgF344-AD rats were impaired in spatial working memory but also showed wide-ranging deficits in exploratory behavior, which may also be indicative of an apathy-like loss of investigatory drive.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings highlight the TgF344-AD rat as a valuable model for studying early apathy-like behavior in AD and underscore the need to consider sex differences in AD research to better understand the prodromal phase of this disease.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnagi.2025.1572956","type":"journal-article","created":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T05:31:53Z","timestamp":1745818313000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Early emergence of motivational and hedonic feeding deficits in the TgF344-AD rat model of Alzheimer\u2019s disease"],"prefix":"10.3389","volume":"17","author":[{"given":"Sean B.","family":"Ostlund","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alisa","family":"Kosheleff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay M","family":"Lueptow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Zhuravka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally A.","family":"Frautschy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoa A.","family":"Lam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nigel T.","family":"Maidment","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3708","DOI":"10.1002\/alz.13809","article-title":"Alzhiemer\u2019s disease facts and figures.","volume":"20","year":"2024","journal-title":"Alzheimer\u2019s Dement."},{"key":"B2","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1016\/j.neubiorev.2019.02.021","article-title":"Novelty processing and memory impairment in Alzheimer\u2019s disease: A review.","volume":"100","author":"Bastin","year":"2019","journal-title":"Neurosci. 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