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@ARTICLE{Candelise:140668,
      author       = {Candelise, Niccolò and Schmitz, Matthias and Llorens,
                      Franc and Villar-Piqué, Anna and Cramm, Maria and Thom,
                      Tobias and Silva-Correia, Susana and da Cunha, José Eriton
                      Gomes and Möbius, Wiebke and Outeiro, Tiago F and Álvarez,
                      Valentina González and Banchelli, Martina and D'Andrea,
                      Cristiano and de Angelis, Marella and Zafar, Saima and
                      Rabano, Alberto and Matteini, Paolo and Zerr, Inga},
      title        = {{S}eeding variability of different alpha synuclein strains
                      in synucleinopathies.},
      journal      = {Annals of neurology},
      volume       = {85},
      number       = {5},
      issn         = {0364-5134},
      address      = {Hoboken, NJ},
      publisher    = {Wiley-Blackwell},
      reportid     = {DZNE-2020-06990},
      pages        = {691-703},
      year         = {2019},
      abstract     = {Currently, the exact reasons why different
                      α-synucleinopathies exhibit variable pathologies and
                      phenotypes are still unknown. A potential explanation may be
                      the existence of distinctive α-synuclein conformers or
                      strains. Here, we intend to analyze the seeding activity of
                      dementia with Lewy bodies (DLB) and Parkinson's disease (PD)
                      brain-derived α-synuclein seeds by real-time
                      quaking-induced conversion (RT-QuIC) and to investigate the
                      structure and morphology of the α-synuclein aggregates
                      generated by RT-QuIC.A misfolded α-synuclein-enriched brain
                      fraction from frontal cortex and substantia nigra pars
                      compacta tissue, isolated by several filtration and
                      centrifugation steps, was subjected to α-synuclein/RT-QuIC
                      analysis. Our study included neuropathologically
                      well-characterized cases with DLB, PD, and controls (Ctrl).
                      Biochemical and morphological analyses of RT-QuIC products
                      were conducted by western blot, dot blot analysis, Raman
                      spectroscopy, atomic force microscopy, and transmission
                      electron microscopy.Independently from the brain region, we
                      observed different seeding kinetics of α-synuclein in the
                      RT-QuIC in patients with DLB compared to PD and Ctrl.
                      Biochemical characterization of the RT-QuIC product
                      indicated the generation of a proteinase K-resistant and
                      fibrillary α-synuclein species in DLB-seeded reactions,
                      whereas PD and control seeds failed in the conversion of
                      wild-type α-synuclein substrate.Structural variances of
                      α-synuclein seeding kinetics and products in DLB and PD
                      indicated, for the first time, the existence of different
                      α-synuclein strains in these groups. Therefore, our study
                      contributes to a better understanding of the clinical
                      heterogeneity among α-synucleinopathies, offers an
                      opportunity for a specific diagnosis, and opens new avenues
                      for the future development of strain-specific therapies. Ann
                      Neurol 2019;85:691-703.},
      keywords     = {Aged / Aged, 80 and over / Brain: metabolism / Brain:
                      pathology / Brain Chemistry: physiology / Female / Humans /
                      Male / Protein Isoforms: analysis / Protein Isoforms:
                      metabolism / Spectrum Analysis, Raman: methods /
                      Synucleinopathies: metabolism / Synucleinopathies: pathology
                      / alpha-Synuclein: analysis / alpha-Synuclein: metabolism},
      cin          = {AG Zerr / Ext UMG Zerr},
      ddc          = {610},
      cid          = {I:(DE-2719)1440011-1 / I:(DE-2719)5000037},
      pnm          = {344 - Clinical and Health Care Research (POF3-344)},
      pid          = {G:(DE-HGF)POF3-344},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:30805957},
      doi          = {10.1002/ana.25446},
      url          = {https://pub.dzne.de/record/140668},
}