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@ARTICLE{Meyer:285731,
      author       = {Meyer, Charlotte Clara and de Mattos, Eduardo Preusser and
                      Burger, Rahel Maria and Blumenstock, Gunnar and Pereira
                      Sena, Priscila and Gordon, Carlos and Zaltzman, Roy and
                      França, Marcondes Cavalcante and Saraiva-Pereira,
                      Maria-Luiza and Cornejo-Olivas, Mario R and Bauer, Peter and
                      Schöls, Ludger and van de Warrenburg, Bart P and Durr,
                      Alexandra and Brice, Alexis and Klockgether, Thomas and
                      Jardim, Laura Bannach and Riess, Olaf and Schmidt, Thorsten},
      collaboration = {Network, EUROSCA},
      othercontributors = {Bauer, Peter and Berciano, José and Boesch, Sylvia and
                          Brice, Alexis and Durr, Alexandra and Forlani, Sylvie and
                          Giunti, Paola and Jacobi, Heike and Klockgether, Thomas and
                          Melegh, Bela and Pandolfo, Massimo and Riess, Olaf and
                          Schmitz-Hübsch, Tanja and Schöls, Ludger and Schulz, Jörg
                          B and Stevanin, Giovanni and Szymanski, Sandra and du
                          Montcel, Sophie Tezenas and Timmann, Dagmar and van de
                          Warrenburg, Bart P C},
      title        = {{A}ssociation of rare apolipoprotein {E} ε4 homozygosity
                      with an earlier age at onset in spinocerebellar ataxia type
                      3.},
      journal      = {Human molecular genetics},
      volume       = {35},
      number       = {5},
      issn         = {0964-6906},
      address      = {Oxford},
      publisher    = {Oxford Univ. Press},
      reportid     = {DZNE-2026-00288},
      pages        = {ddag016},
      year         = {2026},
      abstract     = {Spinocerebellar Ataxia Type 3 (SCA3) is an autosomal
                      dominant neurodegenerative Polyglutamine (polyQ) disease,
                      caused by a cytosine-adenine-guanine (CAG) repeat expansion
                      in the ATXN3 gene, resulting in an expanded polyQ tract in
                      the Ataxin-3 protein. Although the principal genetic
                      determinant of the age at onset (AAO) in polyQ diseases is
                      the expanded CAG repeat length, variability in AAO has been
                      explained only partly, suggesting the existence of
                      additional genetic modifiers. Apolipoprotein E (APOE)
                      haplotypes are associated with the risk of numerous,
                      especially degenerative, diseases. Investigations of a
                      potential role of APOE haplotypes in AAO variability of SCA3
                      have resulted in partly conflicting outcomes, with current
                      evidence lacking power and patient diversity. To further
                      clarify a potential modifying effect of APOE haplotypes on
                      the AAO in SCA3, over 800 SCA3 patients from different
                      origins were enrolled in the present study. While we did not
                      find an association of common APOE haplotypes or singular
                      APOE alleles with AAO in SCA3, rare ε4 homozygosity was
                      linked to an earlier AAO in individuals from Brazil, with a
                      mean disease onset six years earlier than carriers of other
                      APOE haplotypes. Our study thus provides initial evidence
                      for a relevant impact of ε4 homozygosity on disease onset
                      in SCA3 and provides evidence supporting an allele-dosage
                      effect of APOE ε4 in polyQ diseases.},
      keywords     = {Humans / Age of Onset / Female / Male / Machado-Joseph
                      Disease: genetics / Machado-Joseph Disease: epidemiology /
                      Middle Aged / Homozygote / Adult / Haplotypes /
                      Apolipoprotein E4: genetics / Aged / Ataxin-3 / Alleles /
                      Repressor Proteins / Spinocerebellar Ataxia 3 (Other) /
                      genetic modifier (Other) / genetic risk factor (Other) /
                      neurodegeneration (Other) / neurogenetics (Other) /
                      Apolipoprotein E4 (NLM Chemicals) / Ataxin-3 (NLM Chemicals)
                      / ATXN3 protein, human (NLM Chemicals) / Repressor Proteins
                      (NLM Chemicals)},
      cin          = {AG Schöls / Patient Studies (Bonn)},
      ddc          = {570},
      cid          = {I:(DE-2719)5000005 / 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:41854058},
      doi          = {10.1093/hmg/ddag016},
      url          = {https://pub.dzne.de/record/285731},
}