{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T09:34:16Z","timestamp":1787045656101,"version":"build-2736575974"},"posted":{"date-parts":[[2026,8,14]]},"group-title":"Neuroscience","reference-count":68,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["R01NS114651"],"award-info":[{"award-number":["R01NS114651"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["T32NS082145"],"award-info":[{"award-number":["T32NS082145"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["K12GM111726"],"award-info":[{"award-number":["K12GM111726"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National institutes of health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,8,14]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Alzheimer\u2019s Disease (AD) and related dementias (AD\/RDs) impact cortical motor and sensory biology whereas the precise changes to these systems, and their clinical relevance, remain under debate. We hypothesized that cortical representations of complex and simple movements are differently altered during disease progression in 5XFAD mice, a well-established model of AD. Motor cortex somatotopy was determined in 5XFAD and Wild-Type Control (WT Control) mice at 6 and 12 months (mos.) of age using long-duration intracortical microstimulation (LD-ICMS) to systematically identify cortical sites evoking complex and simple forelimb movements. At 6 mos. of age, 5XFAD mice exhibited a significant expansion of motor cortical sites representing simple movements, specifically Elbow Flexion (p=0.0004) and Wrist Flexion (p=0.024). The over-sized territory for Elbow Flexion significantly distinguished 5XFAD from WT mice (Receiver Operating Characteristic [ROC] area under the curve [AUC]= 0.94, p= 0.0009) whereas discriminative performance of Wrist Flexion was a non-significant trend (AUC=0.75, p=0.059). By 12 mos. of age, motor cortex organization was markedly reorganized in 5XFAD mice, with significantly fewer cortical sites evoking complex Advance movement (p&lt;0.0001) as well as simple Shoulder (p=0.0001), Elbow Extension (p=0.024), and Wrist Extension (p=0.003) movements. The number of sites for simple Wrist Flexion was significantly increased (p=0.011) in 12 mo. old 5XFAD mice. At 12 mos., territory size of several of these movement zones highly distinguished 5XFAD from WT mice, including Advance (AUC= 0.96, p= 0.0005), Shoulder (AUC= 0.97, p= 0.0004), Elbow Extension (AUC=0.78, p=0.034), Wrist Extension (AUC=0.85, p= 0.0082), and Wrist Flexion (AUC=0.80, p= 0.023). These findings demonstrate progressive, age-dependent remodeling of motor cortex somatotopy in 5XFAD mice, characterized by early expansion of specific simple movement cortical sites followed by deterioration of both complex and simple motor cortical maps as disease advances. Motor cortex somatotopic remodeling may provide a sensitive biomarker of AD\/RDs progression.<\/jats:p>","DOI":"10.64898\/2026.08.08.743539","type":"posted-content","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T21:30:15Z","timestamp":1786743015000},"source":"Crossref","is-referenced-by-count":0,"title":["Distinct Motor Cortex Somatotopy in Experimental Alzheimer\u2019s Disease"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-8928-3483","authenticated-orcid":false,"given":"SE","family":"Moss","sequence":"first","affiliation":[{"name":"Department of Pathobiology & Integrative Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, Missouri, 65211"},{"name":"Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri, 65211"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7357-2622","authenticated-orcid":false,"given":"CC","family":"Wolsh","sequence":"additional","affiliation":[{"name":"Department of Cellular and Integrative Physiology, Joe R. & Teresa Lozano Long School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas, 78229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"RMII","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Cellular and Integrative Physiology, Joe R. & Teresa Lozano Long School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas, 78229"},{"name":"Department of Biology, Austin College, Sherman, Texas, 75090"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2305-9115","authenticated-orcid":false,"given":"AR","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Cellular and Integrative Physiology, Joe R. & Teresa Lozano Long School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas, 78229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Manchikalapudi","sequence":"additional","affiliation":[{"name":"Department of Pathobiology & Integrative Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, Missouri, 65211"},{"name":"Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri, 65211"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0298-0634","authenticated-orcid":false,"given":"DQ","family":"Beversdorf","sequence":"additional","affiliation":[{"name":"Departments of Neurology, Radiology, and Psychology, William & Nancy Thompson Endowed Chair in Radiology, College of Health Sciences, University of Missouri, Columbia, Missouri, 65212"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2171-1226","authenticated-orcid":false,"given":"L","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Radiology, School of Medicine, University of Missouri, Columbia, Missouri, 65211"},{"name":"Harry S Truman Veterans\u2019 Memorial Hospital, Columbia, Missouri, 65201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7003-1553","authenticated-orcid":false,"given":"JA","family":"Boychuk","sequence":"additional","affiliation":[{"name":"Department of Pathobiology & Integrative Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, Missouri, 65211"},{"name":"Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri, 65211"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026081802200675000_2026.08.08.743539v1.1","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.jalz.2007.04.381","article-title":"Forecasting the global burden of Alzheimer\u2019s disease","volume":"3","year":"2007","journal-title":"Alzheimer\u2019s & dementia"},{"key":"2026081802200675000_2026.08.08.743539v1.2","doi-asserted-by":"crossref","unstructured":"A. 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