{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T04:41:52Z","timestamp":1792557712276,"version":"4.5.0"},"reference-count":38,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Physiological Reports"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Approximately 95% of Alzheimer's disease (AD) diagnoses are sporadic onset, present after the age of 65, and arising from a combination of non\u2010modifiable and modifiable factors. This underscores the potential to identify early systemic changes that may contribute to disease development. One factor may be skeletal muscle atrophy, which has been associated with cognitive decline, although the exact relationship between skeletal muscle and the brain is unknown. Furthermore, whether muscle atrophy begins prior to or after the onset of AD remains elusive. The humanized amyloid\u2010beta knock\u2010in mouse (hA\u03b2\u2010KI) exhibits age\u2010related cognitive decline, insoluble A\u03b2 accumulation, inflammation and microglial activation, making it a useful model of sporadic AD. However, characterization of skeletal muscle changes with aging has yet to be examined. Here, we assess skeletal muscle form and function of the hA\u03b2\u2010KI mouse at 8 and 15\u2009months of age, before and after onset of cognitive decline, through assessment of whole\u2010body lean mass percentage, isolated muscle contraction of the extensor digitorum longus (EDL) and soleus muscle, and fiber type analysis of male and female mice. Whole\u2010body lean mass declined over time in all mice; however, only male hA\u03b2\u2010KI mice had a significant change in body mass and lean mass over the study. At 8\u2010months\u2010old, the isolated EDL of male hA\u03b2\u2010KI mice fatigued faster than the WT mice, but there were no differences at 15\u2009months\u2010old nor fiber type composition at either age. Alternatively, the isolated EDL and soleus of 8\u2010month\u2010old hA\u03b2\u2010KI female mice fatigued slower compared to the WT mice, and there were no differences at 15\u2009months nor fiber type composition at either age. This preliminary characterization work suggests sex\u2010dependent differences in isolated muscle fatigue prior to cognitive decline in the hA\u03b2\u2010KI mouse model of sporadic AD.<\/jats:p>","DOI":"10.14814\/phy2.71153","type":"journal-article","created":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T04:26:11Z","timestamp":1792556771000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Skeletal muscle fatigue resistance is differentially affected in 8\u2010month\u2010old male and female\n                    <scp>hA\u03b2<\/scp>\n                    \u2010\n                    <scp>KI<\/scp>\n                    mice"],"prefix":"10.14814","volume":"14","author":[{"given":"Emily N.","family":"Copeland","sequence":"first","affiliation":[{"name":"Department of Kinesiology Brock University  St. Catharines Ontario Canada"},{"name":"Department of Health Sciences Brock University  St. Catharines Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelin","family":"Melekh","sequence":"additional","affiliation":[{"name":"Department of Health Sciences Brock University  St. Catharines Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4500-3347","authenticated-orcid":false,"given":"Val Andrew","family":"Fajardo","sequence":"additional","affiliation":[{"name":"Department of Kinesiology Brock University  St. Catharines Ontario Canada"},{"name":"Centre for Bone and Muscle Health Brock University  St. Catharines Ontario Canada"},{"name":"Centre for Neurosciences Brock University  St. Catharines Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1577-2658","authenticated-orcid":false,"given":"Rebecca E. K.","family":"MacPherson","sequence":"additional","affiliation":[{"name":"Department of Health Sciences Brock University  St. Catharines Ontario Canada"},{"name":"Centre for Bone and Muscle Health Brock University  St. Catharines Ontario Canada"},{"name":"Centre for Neurosciences Brock University  St. Catharines Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,20]]},"reference":[{"issue":"1","key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1152\/physrev.00015.2007","article-title":"Skeletal muscle fatigue: cellular mechanisms","volume":"88","author":"Allen D. G.","year":"2008","journal-title":"Physiological Reviews"},{"issue":"1","key":"e_1_2_11_3_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-021-22624-z","article-title":"Generation of a humanized Abeta expressing mouse demonstrating aspects of Alzheimer's disease\u2010like pathology","volume":"12","author":"Baglietto\u2010Vargas D.","year":"2021","journal-title":"Nature Communications"},{"issue":"7","key":"e_1_2_11_4_1","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.1111\/jgs.17206","article-title":"Sarcopenia is associated with incident Alzheimer's dementia, mild cognitive impairment, and cognitive decline","volume":"69","author":"Beeri M. 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V.","year":"1988","journal-title":"The Journal of Physiology"},{"issue":"4","key":"e_1_2_11_8_1","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1001\/archneurol.2010.38","article-title":"Reduced lean mass in early Alzheimer disease and its association with brain atrophy","volume":"67","author":"Burns J. 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Regulatory, Integrative and Comparative Physiology"},{"issue":"2","key":"e_1_2_11_14_1","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S1474-4422(12)70291-0","article-title":"Tracking pathophysiological processes in Alzheimer's disease: An updated hypothetical model of dynamic biomarkers","volume":"12","author":"Jack C. R.","year":"2013","journal-title":"The Lancet Neurology"},{"issue":"4","key":"e_1_2_11_15_1","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1007\/s40520-015-0316-5","article-title":"Effects of chronic high\u2010fat feeding on skeletal muscle mass and function in middle\u2010aged mice","volume":"27","author":"Lee S.\u2010R.","year":"2015","journal-title":"Aging Clinical and Experimental Research"},{"issue":"12","key":"e_1_2_11_16_1","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA\u2010seq data with DESeq2","volume":"15","author":"Love M. I.","year":"2014","journal-title":"Genome Biology"},{"issue":"2","key":"e_1_2_11_17_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.isci.2024.108800","article-title":"Behavioral, metabolic, and lipidomic characterization of the 5xFADxTg30 mouse model of Alzheimer's disease","volume":"27","author":"Marshall J. P. 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W.","year":"2025","journal-title":"Nature Medicine"},{"issue":"3","key":"e_1_2_11_38_1","first-page":"38","article-title":"Rate of early onset Alzheimer's disease: A systematic review and meta\u2010analysis","volume":"3","author":"Zhu X. 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