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@ARTICLE{Kluge:1027018,
      author       = {Kluge, Annika and Schaeffer, Eva and Bunk, Josina and
                      Sommerauer, Michael and Röttgen, Sinah and Schulte, Claudia
                      and Roeben, Benjamin and von Thaler, Anna-Katharina and
                      Welzel, Julius and Lucius, Ralph and Heinzel, Sebastian and
                      Xiang, Wei and Eschweiler, Gerhard W. and Maetzler, Walter
                      and Suenkel, Ulrike and Berg, Daniela},
      title        = {{D}etecting {M}isfolded α‐{S}ynuclein in {B}lood {Y}ears
                      before the {D}iagnosis of {P}arkinson's {D}isease},
      journal      = {Movement disorders},
      volume       = {39},
      number       = {8},
      issn         = {0885-3185},
      address      = {New York, NY},
      publisher    = {Wiley},
      reportid     = {FZJ-2024-03584},
      pages        = {1289-1299},
      year         = {2024},
      abstract     = {BackgroundIdentifying individuals with Parkinson's disease
                      (PD) already in the prodromal phase of the disease has
                      become a priority objective for opening a window for early
                      disease-modifying therapies.ObjectiveThe aim was to evaluate
                      a blood-based α-synuclein seed amplification assay (α-syn
                      SAA) as a novel biomarker for diagnosing PD in the prodromal
                      phase.MethodsIn the TREND study (University of Tuebingen)
                      biennial blood samples of n = 1201 individuals
                      with/without increased risk for PD were taken prospectively
                      over 4 to 10 years. We retrospectively analyzed blood
                      samples of 12 participants later diagnosed with PD during
                      the study to detect and amplify pathological α-syn
                      conformers derived from neuronal extracellular vesicles
                      using (1) immunoblot analyses with an antibody against these
                      conformers and (2) an α-syn-SAA. Additionally, blood
                      samples of n = 13 healthy individuals from the TREND
                      cohort and n = 20 individuals with isolated rapid eye
                      movement sleep behavior disorder (iRBD) from the University
                      Hospital Cologne were analyzed.ResultsAll individuals with
                      PD showed positive immunoblots and a positive α-syn SAA at
                      the time of diagnosis. Moreover, all PD patients showed a
                      positive α-syn SAA 1 to 10 years before clinical
                      diagnosis. In the iRBD cohort, $30\%$ showed a positive
                      α-syn SAA. All healthy controls had a negative
                      SAA.ConclusionsWe here demonstrate the possibility to detect
                      and amplify pathological α-syn conformers in peripheral
                      blood up to 10 years before the clinical diagnosis of PD
                      in individuals with and without iRBD. The findings of this
                      study indicate that this blood-based α-syn SAA assay has
                      the potential to serve as a diagnostic biomarker for
                      prodromal PD. © 2024 The Authors. Movement Disorders
                      published by Wiley Periodicals LLC on behalf of
                      International Parkinson and Movement Disorder Society.},
      cin          = {INM-3},
      ddc          = {610},
      cid          = {I:(DE-Juel1)INM-3-20090406},
      pnm          = {5252 - Brain Dysfunction and Plasticity (POF4-525)},
      pid          = {G:(DE-HGF)POF4-5252},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {38651526},
      UT           = {WOS:001206343800001},
      doi          = {10.1002/mds.29766},
      url          = {https://juser.fz-juelich.de/record/1027018},
}