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@ARTICLE{Berger:280023,
      author       = {Berger, Moritz and Garcia-Moreno, Hector and Ferreira,
                      Mónica and Hubener-Schmid, Jeannette and Schaprian, Tamara
                      and Wegner, Philipp and Elter, Tim-Lukas and Teichmann,
                      Kennet M and Santana, Magda M and Grobe-Einsler, Marcus and
                      Oender, Demet and Koyak, Berkan S C and Bernsen, Sarah and
                      Pereira de Almeida, Luís and Silva, Patrick and Ribeiro,
                      Joana Afonso and Cunha, Inês and Gonzalez-Robles, Cristina
                      and Khan, Shamsher and Heslegrave, Amanda and Zetterberg,
                      Henrik and Lima, Manuela and Raposo, Mafalda and Ferreira,
                      Ana F and Vasconcelos, João and van de Warrenburg, Bart P
                      and van Gaalen, Judith and van Prooije, Teije H and de
                      Vries, Jeroen and Schols, Ludger and Riess, Olaf and
                      Synofzik, Matthis and Timmann, Dagmar and Thieme, Andreas
                      and Erdlenbruch, Friedrich and Infante, Jon and
                      Pelayo-Negro, Ana L and Manrique, Leire and Reetz, Kathrin
                      and Dogan, Imis and Oz, Gulin and Joers, James M and
                      Bushara, Khalafalla and Onyike, Chiadikaobi and Povazan,
                      Michal and Jacobi, Heike and Schmahmann, Jeremy D and Ratai,
                      Eva-Maria and Schmid, Matthias and Giunti, Paola and
                      Klockgether, Thomas and Faber, Jennifer},
      title        = {{P}rogression of biological markers in spinocerebellar
                      ataxia type 3: longitudinal analysis of prospective data
                      from the {ESMI} cohort.},
      journal      = {The lancet / Regional health. Europe},
      volume       = {55},
      issn         = {2666-7762},
      address      = {[Amsterdam]},
      publisher    = {Elsevier},
      reportid     = {DZNE-2025-00867},
      pages        = {101339},
      year         = {2025},
      abstract     = {Spinocerebellar ataxia type 3 (SCA3) is an autosomal
                      dominantly inherited adult-onset disease. We aimed to
                      describe longitudinal changes in clinical and biological
                      findings and to identify predictors for clinical
                      progression.We used data from participants enrolled in the
                      ESMI cohort collected between Nov 09, 2016 and July 18,
                      2023. The data freeze included data from 14 sites in five
                      European countries and the United States. We assessed ataxia
                      with the Scale for the Assessment and Rating of Ataxia
                      (SARA). We measured disease-specific mutant ataxin-3 protein
                      (ATXN3) and neurofilament light chain (NfL) in plasma and
                      performed MRIs. Data were analysed by regression modelling
                      on a timescale defined by onset. The onset of abnormality of
                      a marker was defined as the time at which its value, as
                      determined by modelling, exceeded the mean ± 2 SD of
                      healthy controls. To study responsiveness of markers, we
                      determined the sensitivity to change ratios (SCSs).Data from
                      291 SCA3 mutation carriers before and after clinical onset
                      and 121 healthy controls were included. NfL levels became
                      abnormal in SCA3 mutation carriers more than 20 years (-21.5
                      years $[95\%$ CI n.d.-9.5]) before onset. The earliest MRI
                      abnormality was volume loss of medulla oblongata (-4.7 years
                      $[95\%$ CI n.d.-3.3]). The responsiveness of markers
                      depended on the disease stage. Across all stages, pons
                      volume had the highest responsiveness with an SCS of 1.35
                      $[95\%$ CI 1.11-1.78] exceeding that of SARA (0.99 $[95\%$
                      CI 0.88-1.11]). In SCA3, lower age (p = 0.0459 $[95\%$ CI of
                      slope change -0.0018 to 0.0000]) and lower medulla oblongata
                      volume (p < 0.0001 $[95\%$ CI of slope change -0.0298 to
                      -0.0115]) were predictors of SARA progression.Our study
                      provides quantitative information on the progression of
                      biological markers in SCA3 mutation carriers before and
                      after onset of ataxia, and allowed the identification of
                      predictors for clinical progression. Our data could prove
                      useful for the design of future clinical trials.HEU Joint
                      Programme - Neurodegenerative Disease Research (JPND)
                      (Federal Ministry of Education and Research, Germany; The
                      Netherlands Organisation for Health Research and
                      Development; Foundation for Science and Technology,
                      Portugal; Medical Research Council, Regional Fund for
                      Science and Technology, Azores), and Servier. At the US
                      sites this work was in part supported by the National Ataxia
                      Foundation and the National Institute of Neurological
                      Disorders and Stroke (NINDS) grant R01NS080816.},
      keywords     = {ATXN3 (Other) / Biomarker (Other) / Disease modelling
                      (Other) / MRI (Other) / NfL (Other) / Spinocerebellar ataxia
                      (Other) / Staging model (Other)},
      cin          = {Clinical Research (Bonn) / AG Spottke / Clinical Research
                      Platform (CRP) / AG Schöls / AG Gasser / AG Radbruch / AG
                      Schmid Bonn / Patient Studies (Bonn)},
      ddc          = {610},
      cid          = {I:(DE-2719)1011001 / I:(DE-2719)1011103 /
                      I:(DE-2719)1011401 / I:(DE-2719)5000005 / I:(DE-2719)1210000
                      / I:(DE-2719)5000075 / I:(DE-2719)1013028 /
                      I:(DE-2719)1011101},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40678042},
      pmc          = {pmc:PMC12270660},
      doi          = {10.1016/j.lanepe.2025.101339},
      url          = {https://pub.dzne.de/record/280023},
}