{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:48:18Z","timestamp":1760057298532,"version":"build-2065373602"},"reference-count":27,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T00:00:00Z","timestamp":1738281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea (NRF) Grant","award":["2021R1F1A1063874","2024"],"award-info":[{"award-number":["2021R1F1A1063874","2024"]}]},{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT (MIST) of the Republic of Korea","doi-asserted-by":"publisher","award":["2021R1F1A1063874","2024"],"award-info":[{"award-number":["2021R1F1A1063874","2024"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Dankook University Hospital Research Grant","award":["2021R1F1A1063874","2024"],"award-info":[{"award-number":["2021R1F1A1063874","2024"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Emerging evidence from observational studies suggests that lifestyle modifications, particularly moderate-intensity exercise, may confer neuroprotective benefits against dementia, potentially by enhancing brain resistance through clearance mechanisms. Using light-sheet fluorescence microscopy (LSFM) with tissue clearing, we investigated the role of voluntary swimming in ameliorating \u03b2-amyloid pathology in a transgenic Alzheimer\u2019s disease (AD) mouse model. Twenty 52-week-old hAPPsw mice were randomly divided into a 5-week voluntary swimming intervention group and a control group (each n = 10). Each session included a 10-min swim followed by a 10-min rest, escalating from one session per day in the first week to three sessions per day by the fifth week. The excised brains were prepared using tissue-clearing and volume immunostaining with thioflavin-S for \u03b2-amyloid. For LSFM imaging, the individual plaque area and volume, total plaque load, and morphological parameters were quantified via an Imaris-based three-dimensional (3D) volumetric surface model. Visual comparison revealed that the intervention group presented significantly lower \u03b2-amyloid accumulation. The total surface volume of \u03b2-amyloid accumulation in the intervention group was significantly lower than that of the control group (intervention, 122,180,948 \u03bcm3 [105,854,660\u2013169,063,081]; control, 167,201,016 \u03bcm3 [139,367,765\u2013193,535,450]; p = 0.043). There were no significant differences in the morphological parameters, such as ellipticity and sphericity. Our LSFM study demonstrated notable reductions in \u03b2-amyloid, as evidenced by a decrease in total surface volume, in 52-week-old transgenic mice after a 5-week structured swimming program, supporting the notion that even in advanced AD stages, leisure-time voluntary swimming serves as an efficacious intervention for augmenting resistance to pathology.<\/jats:p>","DOI":"10.3390\/ijms26031249","type":"journal-article","created":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T09:16:26Z","timestamp":1738314986000},"page":"1249","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Light-Sheet Fluorescence Imaging Reveals Three-Dimensional Amyloid Burden Reduction Following Five Weeks of Swimming Exercise in Alzheimer\u2019s Mouse"],"prefix":"10.3390","volume":"26","author":[{"given":"Hye Joo","family":"Son","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine, Dankook University Medical Center, Dankook University College of Medicine, Cheonan, Chungnam 31116, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4580-3918","authenticated-orcid":false,"given":"Suk Hyun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Radiology, Hallym University Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul 07441, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1212\/WNL.0000000000005303","article-title":"Resistance vs. resilience to alzheimer disease: Clarifying terminology for preclinical studies","volume":"90","author":"Vemuri","year":"2018","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/S0140-6736(20)30367-6","article-title":"Dementia prevention, intervention, and care: 2020 report of the Lancet commission","volume":"396","author":"Livingston","year":"2020","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1001\/jama.292.12.1447","article-title":"Walking and dementia in physically capable elderly men","volume":"292","author":"Abbott","year":"2004","journal-title":"JAMA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1001\/jama.2015.9617","article-title":"Effect of a 24-month physical activity intervention vs. health education on cognitive outcomes in sedentary older adults: The life randomized trial","volume":"314","author":"Sink","year":"2015","journal-title":"JAMA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1249\/MSS.0000000000001936","article-title":"Physical activity, cognition, and brain outcomes: A review of the 2018 physical activity guidelines","volume":"51","author":"Erickson","year":"2019","journal-title":"Med. 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