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α-Synuclein Pathology in PRKN-Linked Parkinson's Disease: New Insights from a Blood-Based Seed Amplification Assay.
Kluge, Annika; Borsche, Max; Streubel-Gallasch, Linn; Gül, Tugçe; Schaake, Susen; Balck, Alexander; Prasuhn, Jannik; Campbell, Philip; Morris, Huw R; Schapira, Anthony H; Lohmann, Katja; Brüggemann, Norbert; Rakovic, Aleksandar; Seibler, Philip; Basak, A Nazli; Berg, Daniela; Klein, Christine.
Afiliação
  • Kluge A; Department of Neurology, University Hospital Schleswig-Holstein Campus Kiel and Kiel University, Kiel, Germany.
  • Borsche M; Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.
  • Streubel-Gallasch L; Department of Neurology, University Hospital Schleswig-Holstein Campus Lübeck and University of Lübeck, Lübeck, Germany.
  • Gül T; Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.
  • Schaake S; Neurodegeneration Research Laboratory (NDAL), Research Center for Translational Medicine (KUTTAM), University School of Medicine, Istanbul, Turkey.
  • Balck A; Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.
  • Prasuhn J; Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.
  • Campbell P; Department of Neurology, University Hospital Schleswig-Holstein Campus Lübeck and University of Lübeck, Lübeck, Germany.
  • Morris HR; Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.
  • Schapira AH; Department of Neurology, University Hospital Schleswig-Holstein Campus Lübeck and University of Lübeck, Lübeck, Germany.
  • Lohmann K; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London, UK.
  • Brüggemann N; UCL Movement Disorders Center, University College London, London, UK.
  • Rakovic A; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London, UK.
  • Seibler P; UCL Movement Disorders Center, University College London, London, UK.
  • Basak AN; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London, UK.
  • Berg D; UCL Movement Disorders Center, University College London, London, UK.
  • Klein C; Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.
Ann Neurol ; 95(6): 1173-1177, 2024 Jun.
Article em En | MEDLINE | ID: mdl-38546204
ABSTRACT
Pathogenic variants in PRKN cause early-onset Parkinson's disease (PD), while the role of alpha-synuclein in PRKN-PD remains uncertain. One study performed a blood-based alpha-synuclein seed amplification assay (SAA) in PRKN-PD, not detecting seed amplification in 17 PRKN-PD patients. By applying a methodologically different SAA focusing on neuron-derived extracellular vesicles, we demonstrated alpha-synuclein seed amplification in 8 of 13 PRKN-PD patients, challenging the view of PRKN-PD as a non-synucleinopathy. Moreover, we performed blinded replication of the neuron-derived extracellular vesicles-dependent SAA in idiopathic PD patients and healthy controls. In conclusion, blood-based neuron-derived extracellular vesicles-dependent SAA represents a promising biomarker to elucidate the underpinnings of (monogenic) PD. ANN NEUROL 2024;951173-1177.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Limite: Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2024 Tipo de documento: Article
Texto completo
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XML
PubMed Links
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Limite: Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2024 Tipo de documento: Article