{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T19:32:06Z","timestamp":1785526326775,"version":"3.56.0"},"reference-count":73,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T00:00:00Z","timestamp":1755129600000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008005","name":"Yonsei University College of Medicine","doi-asserted-by":"publisher","award":["6\u20102022\u20100073"],"award-info":[{"award-number":["6\u20102022\u20100073"]}],"id":[{"id":"10.13039\/501100008005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>INTRODUCTION<\/jats:title><jats:p>With accumulating evidence that motor manifestations in Alzheimer's disease (AD) may emerge from AD pathology independent of other copathologies, we investigated the neural basis of motor dysfunction under the amyloid\/tau\/neurodegeneration (ATN) framework.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>This study included 125 patients with AD, excluding individuals with severe leukoaraiosis or comorbid Lewy body features beyond Parkinsonism. Associations of ATN burden with motor dysfunction were tested using multivariate regression models, followed by mediation analyses exploring the cognitive contribution to these associations.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Tau burden in the prefrontal, sensorimotor, and parietal regions was associated with motor dysfunction independent of amyloid or neurodegeneration. The effect of parietal tau on motor function was fully mediated by visuospatial dysfunction, whereas prefrontal\/sensorimotor tau exerted direct effects without cognitive mediation.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>Increased tau burden in the sensorimotor and frontoparietal association cortices may elicit motor dysfunction in AD through either cognition\u2010dependent or cognition\u2010independent mechanisms, with effects depending on the affected regions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Tau burden was intimately associated with motor symptoms independent of A\u03b2 or atrophy.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Tau in sensorimotor and frontoparietal association cortices may elicit motor symptoms.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Prefrontal\/sensorimotor tau exerted cognition\u2010independent effects on motor symptoms.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Parietal tau indirectly influenced motor symptoms through visuospatial dysfunction.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Parietal tau\u2010related motor dysfunction may be partly explained by apraxic features.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.70598","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T09:48:52Z","timestamp":1755164932000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Neural basis of motor symptoms in Alzheimer's disease: role of regional tau burden and cognition"],"prefix":"10.1002","volume":"21","author":[{"given":"Han Kyu","family":"Na","sequence":"first","affiliation":[{"name":"Department of Neurology Gangnam Severance Hospital Yonsei University College of Medicine  Seoul South Korea"},{"name":"Department of Neurology Yonsei 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