{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:48:19Z","timestamp":1791931699335,"version":"4.3.4"},"reference-count":21,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,12,5]],"date-time":"2023-12-05T00:00:00Z","timestamp":1701734400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013278","name":"EU Joint Programme \u2013 Neurodegenerative Disease Research","doi-asserted-by":"publisher","award":["739510"],"award-info":[{"award-number":["739510"]}],"id":[{"id":"10.13039\/100013278","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002243","name":"National Ataxia Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002243","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS080816"],"award-info":[{"award-number":["R01NS080816"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:p>Spinocerebellar ataxia type\u20093\/Machado\u2013Joseph disease is the most common autosomal dominant ataxia. In view of the development of targeted therapies, knowledge of early biomarker changes is needed. We analyzed cross\u2010sectional data of 292 spinocerebellar ataxia type\u20093\/Machado\u2013Joseph disease mutation carriers. Blood concentrations of mutant ATXN3 were high before and after ataxia onset, whereas neurofilament light deviated from normal 13.3\u2009years before onset. Pons and cerebellar white matter volumes decreased and deviated from normal 2.2\u2009years and 0.6\u2009years before ataxia onset. We propose a staging model of spinocerebellar ataxia type\u20093\/Machado\u2013Joseph disease that includes a biomarker stage characterized by objective indicators of neurodegeneration before ataxia onset. 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