{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T13:57:54Z","timestamp":1793195874180,"version":"4.5.0"},"reference-count":63,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Alzheimer\u2019s disease (AD) is the most common neurodegenerative disease worldwide, characterized by progressive cognitive decline and, in advanced stages, marked motor impairments. These motor deficits are associated with muscle atrophy, mitochondrial dysfunction, and amyloid-\n                      <jats:italic>\u03b2<\/jats:italic>\n                      (A\u03b2) pathology affecting both motor brain areas and peripheral tissues, ultimately contributing to disability, fall risk, and reduced quality of life. Although physical exercise has been shown to confer cognitive and functional benefits in AD, to date, no studies have directly examined the relationship between motor performance and the underlying pathological mechanisms. This study introduces a novel approach by simultaneously addressing muscle pathology and mitochondrial alterations associated with motor decline.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Twelve-month-old male triple-transgenic (3xTg-AD) and non-transgenic (Non-Tg) mice were assigned to sedentary or exercise groups (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f16 each group). The exercise protocol combined voluntary wheel running and forced treadmill training, 5\u202fdays\/week for 4\u202fmonths. Motor performance was evaluated using open-field, gait analysis, grip strength, and beam walking tests. Post-intervention, histological analyses evaluated A\u03b2 deposition and mitochondrial morphology, biochemical assays assessed mitochondrial function, and ELISA estimated A\u03b2 levels in the brain and muscle.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Physical exercise improved locomotion, balance, and strength in advanced stages of the disease, with modest benefits for memory. Histology showed reduced muscle atrophy and cortical amyloid, but not hippocampal. ELISA detected lower relative levels of A\u03b2 only in the brain. Exercise restored reduced muscle Complex I activity, increased brain Complex IV and ATPase in both tissues, and pronounced changes in mitochondrial morphology in muscle.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study provides the first evidence that physical exercise improves motor function and attenuates muscle and brain pathology in advanced stages of 3xTg-AD, supporting its potential as a complementary therapeutic strategy with translational relevance to humans.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnagi.2026.1730578","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T06:40:20Z","timestamp":1769496020000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Physical exercise mitigates motor and muscular deficits in the 3xTg-AD model of Alzheimer\u2019s disease"],"prefix":"10.3389","volume":"18","author":[{"given":"Jes\u00fas","family":"Andrade-Guerrero","sequence":"first","affiliation":[{"name":"Laboratorio de Investigaci\u00f3n en Neurociencias y Enfermedades Neurodegenerativas (LINEN), Carrera de M\u00e9dico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Aut\u00f3noma de M\u00e9xico","place":["Tlalnepantla, Mexico"]},{"name":"Departamento de Neurobiolog\u00eda del Desarrollo y Neurofisiolog\u00eda, Instituto de Neurobiolog\u00eda, Universidad Nacional Aut\u00f3noma de M\u00e9xico","place":["Quer\u00e9taro, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Le\u00f3n-Arcia","sequence":"additional","affiliation":[{"name":"Laboratorio de Investigaci\u00f3n en Neurociencias y Enfermedades Neurodegenerativas (LINEN), Carrera de M\u00e9dico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Aut\u00f3noma de M\u00e9xico","place":["Tlalnepantla, Mexico"]},{"name":"Departamento de Neurobiolog\u00eda del Desarrollo y Neurofisiolog\u00eda, Instituto de Neurobiolog\u00eda, Universidad Nacional Aut\u00f3noma de M\u00e9xico","place":["Quer\u00e9taro, Mexico"]},{"name":"Posgrado en Ciencias Biol\u00f3gicas, Unidad de Posgrado, Edificio A, 1er Piso, Circuito de Posgrado, Ciudad Universitaria","place":["Ciudad de M\u00e9xico, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar Emiliano","family":"Aparicio-Trejo","sequence":"additional","affiliation":[{"name":"Departamento de Fisiopatolog\u00eda Cardio-Renal, Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez","place":["Ciudad de M\u00e9xico, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Belen","family":"Cuevas-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Departamento de Fisiopatolog\u00eda Cardio-Renal, Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez","place":["Ciudad de M\u00e9xico, Mexico"]},{"name":"CECyT 6, Instituto Polit\u00e9cnico Nacional","place":["Ciudad de M\u00e9xico, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Arias-Carri\u00f3n","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n de Neurociencias, Cl\u00ednica, Instituto Nacional de Rehabilitaci\u00f3n Luis Guillermo Ibarra Ibarra","place":["Ciudad de M\u00e9xico, Mexico"]},{"name":"Tecnol\u00f3gico de Monterrey, Escuela de Medicina y Ciencias de la Salud","place":["Ciudad de M\u00e9xico, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sof\u00eda Y.","family":"D\u00edaz-Miranda","sequence":"additional","affiliation":[{"name":"Departamento de Neurobiolog\u00eda del Desarrollo y Neurofisiolog\u00eda, Instituto de Neurobiolog\u00eda, Universidad Nacional Aut\u00f3noma de M\u00e9xico","place":["Quer\u00e9taro, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis O.","family":"Soto-Rojas","sequence":"additional","affiliation":[{"name":"Laboratorio de Investigaci\u00f3n en Neurociencias y Enfermedades Neurodegenerativas (LINEN), Carrera de M\u00e9dico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Aut\u00f3noma de M\u00e9xico","place":["Tlalnepantla, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,27]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1054","DOI":"10.3390\/brainsci14111054","article-title":"Alzheimer\u2019s disease: understanding motor impairments","volume":"14","author":"Andrade-Guerrero","year":"2024","journal-title":"Brain Sci."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"11134","DOI":"10.3390\/ijms241311134","article-title":"Effects of voluntary physical exercise on the neurovascular unit in a mouse model of Alzheimer\u2019s disease","volume":"24","author":"Andrade-Guerrero","year":"","journal-title":"Int. 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