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In this study, we investigate the impact of intermittent fasting (IF), an alternative strategy of calorie restriction, on cognitive functions and AD\u2010like pathology in a transgenic mouse model of AD. Methods and results: APP\/PS1 mice at 6 months were randomly allocated to two dietary groups: one receiving ad libitum (AL) feeding and the other undergoing IF for 1 month. Y maze, Barnes maze, western blotting, and immunofluorescence were employed. Behavioral assessments revealed that the APP\/PS1\u2010IF group demonstrated notable improvements in cognitive function compared to the AL group. Further analysis showed that microglia in the APP\/PS1\u2010IF mice exhibited enhanced phagocytic activity, characterized by prominent enlargement of soma and reduced complexity of their processes. Importantly, IF significantly decreased the accumulation of lipid droplets (LDs) within microglia. These microglia with less LDs may contribute to enhanced \u03b2\u2010amyloid (A\u03b2) phagocytosis, thereby ameliorating A\u03b2 deposition in the brains of APP\/PS1\u2010IF mice. Conclusion: Our findings demonstrate that IF ameliorates amyloid deposition and cognitive deficits in the AD model mice, which is associated with the reduction of LDs within microglia, providing support for the use of the dietary intervention against AD pathology.<\/jats:p>","DOI":"10.1002\/mnfr.202400660","type":"journal-article","created":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T10:06:48Z","timestamp":1737540408000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Intermittent Fasting Ameliorates \u03b2\u2010Amyloid Deposition and Cognitive Impairment Accompanied by Decreased Lipid Droplet Aggregation Within Microglia in an Alzheimer's Disease Model"],"prefix":"10.1002","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-0641-8917","authenticated-orcid":false,"given":"Liangwei","family":"Wu","sequence":"first","affiliation":[{"name":"Institutes of Biomedical Sciences School of Medicine 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