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@ARTICLE{Schmitz:164069,
      author       = {Schmitz, Matthias and Villar-Piqué, Anna and Hermann,
                      Peter and Escaramís, Geòrgia and Calero, Miguel and Chen,
                      Cao and Kruse, Niels and Cramm, Maria and Golanska, Ewa and
                      Sikorska, Beata and Liberski, Pawel P and Pocchiari,
                      Maurizio and Lange, Peter and Stehmann, Christiane and
                      Sarros, Shannon and Martí, Eulàlia and Baldeiras, Inês
                      and Santana, Isabel and Žáková, Dana and Mitrová, Eva
                      and Dong, Xiao-Ping and Collins, Steven and Poleggi, Anna
                      and Ladogana, Anna and Mollenhauer, Brit and Kovacs, Gabor G
                      and Geschwind, Michael D and Sánchez-Valle, Raquel and
                      Zerr, Inga and Llorens Torres, Francesc Josep},
      title        = {{D}iagnostic accuracy of cerebrospinal fluid biomarkers in
                      genetic prion diseases.},
      journal      = {Brain},
      volume       = {145},
      number       = {2},
      issn         = {0006-8950},
      address      = {Oxford},
      publisher    = {Oxford Univ. Press},
      reportid     = {DZNE-2022-00732},
      pages        = {700 - 712},
      year         = {2022},
      note         = {(CC BY-NC)},
      abstract     = {Genetic prion diseases are a rare and diverse group of
                      fatal neurodegenerative disorders caused by pathogenic
                      sequence variations in the prion protein gene, PRNP. Data on
                      CSF biomarkers in patients with genetic prion diseases are
                      limited and conflicting results have been reported for
                      unclear reasons. Here, we aimed to analyse the diagnostic
                      accuracy of CSF biomarkers currently used in prion clinical
                      diagnosis in 302 symptomatic genetic prion disease cases
                      from 11 prion diagnostic centres, encompassing a total of 36
                      different pathogenic sequence variations within the open
                      reading frame of PRNP. CSF samples were assessed for the
                      surrogate markers of neurodegeneration, 14-3-3 protein
                      (14-3-3), total-tau protein (t-tau) and α-synuclein and for
                      prion seeding activity through the real-time quaking-induced
                      conversion assay. Biomarker results were compared with those
                      obtained in healthy and neurological controls. For the most
                      prevalent PRNP pathogenic sequence variations, biomarker
                      accuracy and associations between biomarkers, demographic
                      and genetic determinants were assessed. Additionally, the
                      prognostic value of biomarkers for predicting total disease
                      duration from symptom onset to death was investigated. High
                      sensitivity of the four biomarkers was detected for genetic
                      Creutzfeldt-Jakob disease associated with the E200K and
                      V210I mutations, but low sensitivity was observed for
                      mutations associated with Gerstmann-Sträussler-Scheinker
                      syndrome and fatal familial insomnia. All biomarkers showed
                      good to excellent specificity using the standard cut-offs
                      often used for sporadic Creutzfeldt-Jakob disease. In
                      genetic prion diseases related to octapeptide repeat
                      insertions, the biomarker sensitivity correlated with the
                      number of repeats. New genetic prion disease-specific
                      cut-offs for 14-3-3, t-tau and α-synuclein were calculated.
                      Disease duration in genetic Creutzfeldt-Jakob disease-E200K,
                      Gerstmann-Sträussler-Scheinker-P102L and fatal familial
                      insomnia was highly dependent on PRNP codon 129 MV
                      polymorphism and was significantly associated with biomarker
                      levels. In a large cohort of genetic prion diseases, the
                      simultaneous analysis of CSF prion disease biomarkers
                      allowed the determination of new mutation-specific cut-offs
                      improving the discrimination of genetic prion disease cases
                      and unveiled genetic prion disease-specific associations
                      with disease duration.},
      keywords     = {Biomarkers: cerebrospinal fluid / Creutzfeldt-Jakob
                      Syndrome: diagnosis / Creutzfeldt-Jakob Syndrome: genetics /
                      Humans / Insomnia, Fatal Familial: genetics / Prion
                      Diseases: diagnosis / Prion Diseases: genetics / Prion
                      Proteins: genetics / Prions: genetics / alpha-Synuclein /
                      biomarker (Other) / cerebrospinal fluid (Other) / diagnostic
                      marker (Other) / genetic prion diseases (Other) / Biomarkers
                      (NLM Chemicals) / Prion Proteins (NLM Chemicals) / Prions
                      (NLM Chemicals) / alpha-Synuclein (NLM Chemicals)},
      cin          = {AG Zerr / Ext UMG Zerr},
      ddc          = {610},
      cid          = {I:(DE-2719)1440011-1 / I:(DE-2719)5000037},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:35288744},
      pmc          = {pmc:PMC9014756},
      doi          = {10.1093/brain/awab350},
      url          = {https://pub.dzne.de/record/164069},
}