Stage‐Dependent Biomarker Changes in Spinocerebellar Ataxia Type 3
Jennifer Faber, Moritz Berger, Carlo Wilke, Jeannette Hübener‐Schmid, Tamara Schaprian, Magda M. Santana, Marcus Grobe‐Einsler, Demet Önder, Berkan Koyak, Paola Giunti, Héctor García‐Moreno, Cristina Gonzalez‐Robles, Manuela Lima, Mafalda Raposo, Ana Rosa Vieira Melo, Luís Pereira de Almeida, Patrick Silva, Maria M Pinto, Bart P.C. van de Warrenburg, Judith van Gaalen, Jeroen de Vries, Gülin Öz, James M. Joers, Matthis Synofzik, Lüdger Schöls, Olaf Rieß, Jon Infante, Leire Manrique, Dagmar Timmann, Andreas Thieme, Heike Jacobi, Kathrin Reetz, Imis Dogan, Chiadikaobi Onyike, Michal Považan, Jeremy D. Schmahmann, Eva‐Maria Ratai, Matthias Schmid, Thomas Klockgether
Abstract
Spinocerebellar ataxia type 3/Machado-Joseph 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-sectional data of 292 spinocerebellar ataxia type 3/Machado-Joseph disease mutation carriers. Blood concentrations of mutant ATXN3 were high before and after ataxia onset, whereas neurofilament light deviated from normal 13.3 years before onset. Pons and cerebellar white matter volumes decreased and deviated from normal 2.2 years and 0.6 years before ataxia onset. We propose a staging model of spinocerebellar ataxia type 3/Machado-Joseph disease that includes a biomarker stage characterized by objective indicators of neurodegeneration before ataxia onset. ANN NEUROL 2024;95:400-406.