{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T07:01:35Z","timestamp":1790146895374,"version":"4.0.1"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"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>Gait alterations have been proposed as functional indicators of neural dysfunction in Alzheimer's disease; however, their ability to capture disease-associated locomotor changes in preclinical models remains insufficiently characterized.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this study, we applied a neuroinformatics framework combining markerless pose estimation, kinematic feature extraction, conventional statistical analysis, supervised machine learning, and model interpretability to characterize gait alterations in the 3xTg-AD mouse model. Two complementary analyses were performed: cross-sectional genotype classification at 12 months of age in 46 mice (3xTg-AD,\n                      <jats:italic>n<\/jats:italic>\n                      = 22; 3xTg-WT,\n                      <jats:italic>n<\/jats:italic>\n                      = 24) and longitudinal assessment of 31 paired surviving animals re-evaluated at 16 months (3xTg-AD,\n                      <jats:italic>n<\/jats:italic>\n                      = 15; 3xTg-WT,\n                      <jats:italic>n<\/jats:italic>\n                      = 16).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>At 12 months, gait features provided moderate-to-good genotype discrimination, with Logistic Regression achieving the highest balanced performance (AUC = 0.82) and showing relevant contributions from Duty Factor, Allometric Stride Length, Allometric Step Width, and Speed. In the longitudinal cohort, classification performance was more limited (Random Forest, AUC = 0.61), likely reflecting the combined influence of physiological aging, genotype-associated change, selective survival, and task re-exposure. Nevertheless, conventional statistical analysis and SHAP-based model interpretation consistently identified longitudinal changes in Allometric Stride Length and Normalized Coordination Instability as relevant contributors to genotype-associated locomotor divergence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings suggest that computational gait analysis can capture relevant alterations in locomotor organization in the 3xTg-AD model, with cross-sectional differences associated with distributed spatiotemporal features and longitudinal changes showing a stronger contribution of stride- and coordination-related variables.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnagi.2026.1879487","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T06:18:28Z","timestamp":1790144308000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Computational gait analysis in the 3xTg-AD mouse model: evidence of progressive alterations in locomotor coordination"],"prefix":"10.3389","volume":"18","author":[{"given":"Lidia","family":"Castillo Mariqueo","sequence":"first","affiliation":[{"name":"Faculty of Rehabilitation Sciences, School of Physical Therapy, Exercise and Rehabilitation Sciences Institute, Universidad Andres Bello","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mart\u00edn","family":"Valdivia Gallardo","sequence":"additional","affiliation":[{"name":"Facultad de Ingenier\u00eda","place":["Universidad Andr\u00e9s Bello, Instituto de Tecnolog\u00eda para la Innovaci\u00f3n en Salud y Bienestar, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydia","family":"Gim\u00e9nez Llort","sequence":"additional","affiliation":[{"name":"Institut de Neuroci\u00e9ncies, Universitat Aut\u00f3noma de Barcelona","place":["Barcelona, Spain"]},{"name":"Department of Psychiatry and Forensic Medicine, School of Medicine, Universitat Aut\u00f3noma de Barcelona","place":["Barcelona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Taramasco Toro","sequence":"additional","affiliation":[{"name":"Facultad de Ingenier\u00eda","place":["Universidad Andr\u00e9s Bello, Instituto de Tecnolog\u00eda para la Innovaci\u00f3n en Salud y Bienestar, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Chahuan Moyano","sequence":"additional","affiliation":[{"name":"Facultad de Ingenier\u00eda","place":["Universidad Andr\u00e9s Bello, Instituto de Tecnolog\u00eda para la Innovaci\u00f3n en Salud y Bienestar, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Robles Cruz","sequence":"additional","affiliation":[{"name":"Facultad de Ingenier\u00eda","place":["Universidad Andr\u00e9s Bello, Instituto de Tecnolog\u00eda para la Innovaci\u00f3n en Salud y Bienestar, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1177\/13872877261430001","article-title":"Gait and movement analysis for discrimination between people with dementia and healthy control persons based on pose estimation and machine learning","volume":"111","author":"Al-Hammadi","year":"2024","journal-title":"J. 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