{"doi":"10.3389/fnagi.2025.1572956","title":"Early emergence of motivational and hedonic feeding deficits in the TgF344-AD rat model of Alzheimer’s disease","abstract":"Introduction: Alzheimer's 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. Methods: 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 (3-4 months), intermediate (6-7 months), and later (9-10 months) stages of adulthood. Results: We found that female TgF344-AD rats exhibited early and persistent deficits in motivational and hedonic feeding, emerging at 3-4 months and 6-7 months, respectively. During a battery of cognitive tests conducted after 12-14 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. Conclusion: 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.","journal":"Frontiers in Aging Neuroscience","year":2025,"id":518291,"datarank":0.31191623125197543,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.0,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9613,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1385717,"name":"Grace Chen","orcid":"0000-0003-1049-1571","position":1,"is_corresponding":false},{"id":1385718,"name":"Alisa R. Kosheleff","orcid":"0000-0002-5738-7221","position":2,"is_corresponding":false},{"id":756267,"name":"Lindsay M. Lueptow","orcid":"0000-0001-5343-7618","position":3,"is_corresponding":false},{"id":819388,"name":"Irina Zhuravka","orcid":null,"position":4,"is_corresponding":false},{"id":344634,"name":"Sally A. Frautschy","orcid":"0000-0003-0194-0363","position":5,"is_corresponding":false},{"id":494677,"name":"Hoa A. Lam","orcid":null,"position":6,"is_corresponding":false},{"id":199091,"name":"Nigel T. Maidment","orcid":null,"position":7,"is_corresponding":false},{"id":378585,"name":"Sean B. Ostlund","orcid":"0000-0003-1635-3911","position":0,"is_corresponding":true}],"reference_count":97,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:49:09.679930Z","pmid":"40357232","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}