000280023 001__ 280023
000280023 005__ 20250824001715.0
000280023 0247_ $$2doi$$a10.1016/j.lanepe.2025.101339
000280023 0247_ $$2pmid$$apmid:40678042
000280023 0247_ $$2pmc$$apmc:PMC12270660
000280023 0247_ $$2altmetric$$aaltmetric:178874846
000280023 037__ $$aDZNE-2025-00867
000280023 041__ $$aEnglish
000280023 082__ $$a610
000280023 1001_ $$aBerger, Moritz$$b0
000280023 245__ $$aProgression of biological markers in spinocerebellar ataxia type 3: longitudinal analysis of prospective data from the ESMI cohort.
000280023 260__ $$a[Amsterdam]$$bElsevier$$c2025
000280023 3367_ $$2DRIVER$$aarticle
000280023 3367_ $$2DataCite$$aOutput Types/Journal article
000280023 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1755681458_25773
000280023 3367_ $$2BibTeX$$aARTICLE
000280023 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000280023 3367_ $$00$$2EndNote$$aJournal Article
000280023 520__ $$aSpinocerebellar 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.
000280023 536__ $$0G:(DE-HGF)POF4-353$$a353 - Clinical and Health Care Research (POF4-353)$$cPOF4-353$$fPOF IV$$x0
000280023 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
000280023 650_7 $$2Other$$aATXN3
000280023 650_7 $$2Other$$aBiomarker
000280023 650_7 $$2Other$$aDisease modelling
000280023 650_7 $$2Other$$aMRI
000280023 650_7 $$2Other$$aNfL
000280023 650_7 $$2Other$$aSpinocerebellar ataxia
000280023 650_7 $$2Other$$aStaging model
000280023 7001_ $$aGarcia-Moreno, Hector$$b1
000280023 7001_ $$0P:(DE-2719)9003289$$aFerreira, Mónica$$b2$$udzne
000280023 7001_ $$aHubener-Schmid, Jeannette$$b3
000280023 7001_ $$0P:(DE-2719)2812594$$aSchaprian, Tamara$$b4$$udzne
000280023 7001_ $$0P:(DE-2719)9002349$$aWegner, Philipp$$b5$$udzne
000280023 7001_ $$0P:(DE-2719)9001258$$aElter, Tim-Lukas$$b6$$udzne
000280023 7001_ $$0P:(DE-2719)9002253$$aTeichmann, Kennet M$$b7$$udzne
000280023 7001_ $$aSantana, Magda M$$b8
000280023 7001_ $$0P:(DE-2719)9001510$$aGrobe-Einsler, Marcus$$b9$$udzne
000280023 7001_ $$0P:(DE-2719)9000685$$aOender, Demet$$b10$$udzne
000280023 7001_ $$0P:(DE-2719)9001550$$aKoyak, Berkan S C$$b11$$udzne
000280023 7001_ $$0P:(DE-2719)9000485$$aBernsen, Sarah$$b12$$udzne
000280023 7001_ $$aPereira de Almeida, Luís$$b13
000280023 7001_ $$aSilva, Patrick$$b14
000280023 7001_ $$aRibeiro, Joana Afonso$$b15
000280023 7001_ $$aCunha, Inês$$b16
000280023 7001_ $$aGonzalez-Robles, Cristina$$b17
000280023 7001_ $$aKhan, Shamsher$$b18
000280023 7001_ $$aHeslegrave, Amanda$$b19
000280023 7001_ $$aZetterberg, Henrik$$b20
000280023 7001_ $$aLima, Manuela$$b21
000280023 7001_ $$aRaposo, Mafalda$$b22
000280023 7001_ $$aFerreira, Ana F$$b23
000280023 7001_ $$aVasconcelos, João$$b24
000280023 7001_ $$avan de Warrenburg, Bart P$$b25
000280023 7001_ $$avan Gaalen, Judith$$b26
000280023 7001_ $$avan Prooije, Teije H$$b27
000280023 7001_ $$ade Vries, Jeroen$$b28
000280023 7001_ $$0P:(DE-2719)2810795$$aSchols, Ludger$$b29$$udzne
000280023 7001_ $$aRiess, Olaf$$b30
000280023 7001_ $$0P:(DE-2719)2811275$$aSynofzik, Matthis$$b31$$udzne
000280023 7001_ $$aTimmann, Dagmar$$b32
000280023 7001_ $$aThieme, Andreas$$b33
000280023 7001_ $$aErdlenbruch, Friedrich$$b34
000280023 7001_ $$aInfante, Jon$$b35
000280023 7001_ $$aPelayo-Negro, Ana L$$b36
000280023 7001_ $$aManrique, Leire$$b37
000280023 7001_ $$aReetz, Kathrin$$b38
000280023 7001_ $$aDogan, Imis$$b39
000280023 7001_ $$aOz, Gulin$$b40
000280023 7001_ $$aJoers, James M$$b41
000280023 7001_ $$aBushara, Khalafalla$$b42
000280023 7001_ $$aOnyike, Chiadikaobi$$b43
000280023 7001_ $$aPovazan, Michal$$b44
000280023 7001_ $$aJacobi, Heike$$b45
000280023 7001_ $$aSchmahmann, Jeremy D$$b46
000280023 7001_ $$aRatai, Eva-Maria$$b47
000280023 7001_ $$0P:(DE-2719)2811245$$aSchmid, Matthias$$b48$$udzne
000280023 7001_ $$aGiunti, Paola$$b49
000280023 7001_ $$0P:(DE-2719)2810314$$aKlockgether, Thomas$$b50$$udzne
000280023 7001_ $$0P:(DE-2719)2811327$$aFaber, Jennifer$$b51$$eLast author$$udzne
000280023 773__ $$0PERI:(DE-600)3055963-7$$a10.1016/j.lanepe.2025.101339$$gVol. 55, p. 101339 -$$p101339$$tThe lancet / Regional health. Europe$$v55$$x2666-7762$$y2025
000280023 8564_ $$uhttps://pub.dzne.de/record/280023/files/DZNE-2025-00867%20SUP.docx
000280023 8564_ $$uhttps://pub.dzne.de/record/280023/files/DZNE-2025-00867.pdf$$yOpenAccess
000280023 8564_ $$uhttps://pub.dzne.de/record/280023/files/DZNE-2025-00867%20SUP.doc
000280023 8564_ $$uhttps://pub.dzne.de/record/280023/files/DZNE-2025-00867%20SUP.odt
000280023 8564_ $$uhttps://pub.dzne.de/record/280023/files/DZNE-2025-00867%20SUP.pdf
000280023 8564_ $$uhttps://pub.dzne.de/record/280023/files/DZNE-2025-00867.pdf?subformat=pdfa$$xpdfa$$yOpenAccess
000280023 909CO $$ooai:pub.dzne.de:280023$$pdnbdelivery$$pdriver$$pVDB$$popen_access$$popenaire
000280023 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)9003289$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b2$$kDZNE
000280023 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2812594$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b4$$kDZNE
000280023 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)9002349$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b5$$kDZNE
000280023 9101_ $$0I:(DE-HGF)0$$6P:(DE-2719)9001258$$aExternal Institute$$b6$$kExtern
000280023 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)9002253$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b7$$kDZNE
000280023 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)9001510$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b9$$kDZNE
000280023 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)9000685$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b10$$kDZNE
000280023 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)9001550$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b11$$kDZNE
000280023 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)9000485$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b12$$kDZNE
000280023 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2810795$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b29$$kDZNE
000280023 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2811275$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b31$$kDZNE
000280023 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2811245$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b48$$kDZNE
000280023 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2810314$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b50$$kDZNE
000280023 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2811327$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b51$$kDZNE
000280023 9131_ $$0G:(DE-HGF)POF4-353$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vClinical and Health Care Research$$x0
000280023 9141_ $$y2025
000280023 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2024-12-20
000280023 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2024-12-20
000280023 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2024-12-20
000280023 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2024-12-20
000280023 915__ $$0LIC:(DE-HGF)CCBYNCND4$$2HGFVOC$$aCreative Commons Attribution-NonCommercial-NoDerivs CC BY-NC-ND 4.0
000280023 915__ $$0StatID:(DE-HGF)9920$$2StatID$$aIF >= 20$$bLANCET REG HEALTH-EU : 2022$$d2024-12-20
000280023 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bLANCET REG HEALTH-EU : 2022$$d2024-12-20
000280023 915__ $$0StatID:(DE-HGF)1180$$2StatID$$aDBCoverage$$bCurrent Contents - Social and Behavioral Sciences$$d2024-12-20
000280023 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal$$d2023-04-12T14:52:56Z
000280023 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ$$d2023-04-12T14:52:56Z
000280023 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2024-12-20
000280023 915__ $$0StatID:(DE-HGF)0700$$2StatID$$aFees$$d2024-12-20
000280023 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2024-12-20
000280023 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess
000280023 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bDOAJ : Anonymous peer review$$d2023-04-12T14:52:56Z
000280023 915__ $$0StatID:(DE-HGF)0561$$2StatID$$aArticle Processing Charges$$d2024-12-20
000280023 915__ $$0StatID:(DE-HGF)0130$$2StatID$$aDBCoverage$$bSocial Sciences Citation Index$$d2024-12-20
000280023 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2024-12-20
000280023 915__ $$0StatID:(DE-HGF)1110$$2StatID$$aDBCoverage$$bCurrent Contents - Clinical Medicine$$d2024-12-20
000280023 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2024-12-20
000280023 9201_ $$0I:(DE-2719)1011001$$kClinical Research (Bonn)$$lClinical Research Coordination$$x0
000280023 9201_ $$0I:(DE-2719)1011103$$kAG Spottke$$lClinical Research Platform (CRP)$$x1
000280023 9201_ $$0I:(DE-2719)1011401$$kClinical Research Platform (CRP)$$lClinical Research Platform (CRP)$$x2
000280023 9201_ $$0I:(DE-2719)5000005$$kAG Schöls$$lClinical Neurogenetics$$x3
000280023 9201_ $$0I:(DE-2719)1210000$$kAG Gasser$$lParkinson Genetics$$x4
000280023 9201_ $$0I:(DE-2719)5000075$$kAG Radbruch$$lClinical Neuroimaging$$x5
000280023 9201_ $$0I:(DE-2719)1013028$$kAG Schmid Bonn$$lMathematics, statistics and informatics methods for support of population studies and clinical research$$x6
000280023 9201_ $$0I:(DE-2719)1011101$$kPatient Studies (Bonn)$$lPatient Studies (Bonn)$$x7
000280023 980__ $$ajournal
000280023 980__ $$aVDB
000280023 980__ $$aUNRESTRICTED
000280023 980__ $$aI:(DE-2719)1011001
000280023 980__ $$aI:(DE-2719)1011103
000280023 980__ $$aI:(DE-2719)1011401
000280023 980__ $$aI:(DE-2719)5000005
000280023 980__ $$aI:(DE-2719)1210000
000280023 980__ $$aI:(DE-2719)5000075
000280023 980__ $$aI:(DE-2719)1013028
000280023 980__ $$aI:(DE-2719)1011101
000280023 9801_ $$aFullTexts