{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T01:32:02Z","timestamp":1787967122766,"version":"build-2784847793"},"reference-count":70,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG080731"],"award-info":[{"award-number":["R01AG080731"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["K02AG088474"],"award-info":[{"award-number":["K02AG088474"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R00AG070104"],"award-info":[{"award-number":["R00AG070104"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG062548"],"award-info":[{"award-number":["R01AG062548"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG069781"],"award-info":[{"award-number":["R01AG069781"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P20GM144269"],"award-info":[{"award-number":["P20GM144269"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Alzheimer's disease (AD) progresses along a continuum for years to possibly decades prior to cognitive decline. Although AD is primarily an age\u2010related brain pathology, increasing evidence indicates dysfunction in peripheral nerves and skeletal muscle may manifest early in the disease progression. However, the underlying cause(s) for peripheral nerve dysfunction leading to impaired skeletal muscle torque production are not understood. Sciatic nerves from 5xFAD and wild\u2010type (WT) mice were analyzed by tandem mass tag (TMT)\u2010labeled proteomics at 3, 4, and 7\u2009months, identifying proteome remodeling coincides with functional declines at 4\u2009months particularly in pathways linked to mitochondrial turnover, calcium handling, and inflammation. We hypothesized either voluntary wheel running or donepezil treatment, begun prior to neuromuscular decline, would delay manifestation of neuromuscular impairment in 5xFAD mice. Separate cohorts, using 3\u2010month\u2010old 5xFAD mice and WT littermates, were given voluntary wheel access for 4\u2009weeks or treated with the acetylcholinesterase inhibitor donepezil. We assessed tibial nerve stimulated plantar flexion torque and sciatic nerve compound (motor) neuron action potential (CNAP) in\u00a0vivo at 4\u2009months. Both exercise and donepezil attenuated in\u00a0vivo nerve\u2010stimulated muscle torque and CNAP dysfunction. Further, both exercise and donepezil attenuated the proteomic remodeling of the sciatic nerve through both shared and independent mechanisms that converged on mitochondria\u2010centric pathways. Our findings in the 5xFAD model of AD support the notion that early phenotypes of AD are evident in the periphery that may have implications for timing of interventions.<\/jats:p>","DOI":"10.1111\/acel.70595","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T09:20:14Z","timestamp":1781601614000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Age\u2010Dependent Remodeling of the Sciatic Nerve Proteome in\n                    <scp>5xFAD<\/scp>\n                    Mice Can Be Attenuated by Exercise or Donepezil Treatment to Maintain Neuromuscular Function"],"prefix":"10.1111","volume":"25","author":[{"given":"Matthew H.","family":"Brisendine","sequence":"first","affiliation":[{"name":"Department of Human Nutrition, Foods, and Exercise Virginia Polytechnic Institute and State University  Blacksburg Virginia 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State University  Blacksburg Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel S.","family":"Braxton","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Virginia Polytechnic Institute and State University  Blacksburg Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shelby N.","family":"Henry","sequence":"additional","affiliation":[{"name":"Department of Human Nutrition, Foods, and Exercise Virginia Polytechnic Institute and State University  Blacksburg Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin S.","family":"McCoin","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology and Physiology and Department of Internal Medicine\u2010Division of Endocrinology University of Kansas Medical Center  Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P.","family":"Thyfault","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology and Physiology and Department of Internal Medicine\u2010Division of Endocrinology University of Kansas Medical Center  Kansas City Kansas USA"},{"name":"Department of Neurology and KU Alzheimer's Disease Research Center University of Kansas Medical Center  Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill K.","family":"Morris","sequence":"additional","affiliation":[{"name":"Department of Neurology and KU Alzheimer's Disease Research Center University of Kansas Medical Center  Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Poelzing","sequence":"additional","affiliation":[{"name":"Translational Biology, Medicine, and Health Program Virginia Polytechnic Institute and State University  Roanoke Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert 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