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Aggregation-resistant alpha-synuclein tetramers are reduced in the blood of Parkinson's patients.
de Boni, Laura; Wallis, Amber; Hays Watson, Aurelia; Ruiz-Riquelme, Alejandro; Leyland, Louise-Ann; Bourinaris, Thomas; Hannaway, Naomi; Wüllner, Ullrich; Peters, Oliver; Priller, Josef; Falkenburger, Björn H; Wiltfang, Jens; Bähr, Mathias; Zerr, Inga; Bürger, Katharina; Perneczky, Robert; Teipel, Stefan; Löhle, Matthias; Hermann, Wiebke; Schott, Björn-Hendrik; Brockmann, Kathrin; Spottke, Annika; Haustein, Katrin; Breuer, Peter; Houlden, Henry; Weil, Rimona S; Bartels, Tim.
Afiliación
  • de Boni L; UK Dementia Research Institute, University College London, London, W1T 7NF, UK.
  • Wallis A; Institute of Aerospace Medicine, German Aerospace Center (DLR), 51147, Cologne, Germany.
  • Hays Watson A; Department of Neurology, University Hospital Bonn, 53127, Bonn, Germany.
  • Ruiz-Riquelme A; UK Dementia Research Institute, University College London, London, W1T 7NF, UK.
  • Leyland LA; UK Dementia Research Institute, University College London, London, W1T 7NF, UK.
  • Bourinaris T; University of Santiago de Compostela, 15705, Santiago de Compostela, Galicia, Spain.
  • Hannaway N; Dementia Research Center, Institute of Neurology, University College London, Queen Square, London, WC1N 3BG, UK.
  • Wüllner U; Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, WC1N 3BG, UK.
  • Peters O; Dementia Research Center, Institute of Neurology, University College London, Queen Square, London, WC1N 3BG, UK.
  • Priller J; German Center for Neurodegenerative Diseases (DZNE), 53127, Bonn, Germany.
  • Falkenburger BH; Departments of Neurology and Neurodegenerative Diseases, University Bonn, 53127, Bonn, Germany.
  • Wiltfang J; Institute of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 12203, Berlin, Germany.
  • Bähr M; German Center for Neurodegenerative Diseases (DZNE), 10117, Berlin, Germany.
  • Zerr I; German Center for Neurodegenerative Diseases (DZNE), 10117, Berlin, Germany.
  • Bürger K; Department of Psychiatry and Psychotherapy, Charité, Charitéplatz 1, 10117, Berlin, Germany.
  • Perneczky R; University of Edinburgh and UK DRI, Edinburgh, EH16 4SB, UK.
  • Teipel S; School of Medicine, Technical University of Munich, Department of Psychiatry and Psychotherapy, 81675, Munich, Germany.
  • Löhle M; German Center for Neurodegenerative Diseases (DZNE), 01307, Dresden, Germany.
  • Hermann W; Department of Neurology, University Hospital Carl Gustav Carus, Dresden University of Technology, 01307, Dresden, Germany.
  • Schott BH; German Center for Neurodegenerative Diseases (DZNE), 37075, Goettingen, Germany.
  • Brockmann K; Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, Georg August University, 37075, Göttingen, Germany.
  • Spottke A; Neurosciences and Signaling Group, Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, 3810-193, Aveiro, Portugal.
  • Haustein K; German Center for Neurodegenerative Diseases (DZNE), 37075, Goettingen, Germany.
  • Breuer P; Department of Neurology, University Medical Center, Georg August University, 37075, Göttingen, Germany.
  • Houlden H; Cluster of Excellence Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), University Medical Center Göttingen, 37075, Göttingen, Germany.
  • Weil RS; German Center for Neurodegenerative Diseases (DZNE), 37075, Goettingen, Germany.
  • Bartels T; Department of Neurology, University Medical Center, Georg August University, 37075, Göttingen, Germany.
EMBO Mol Med ; 16(7): 1657-1674, 2024 Jul.
Article en En | MEDLINE | ID: mdl-38839930
ABSTRACT
Synucleinopathies such as Parkinson's disease (PD) are defined by the accumulation and aggregation of the α-synuclein protein in neurons, glia and other tissues. We have previously shown that destabilization of α-synuclein tetramers is associated with familial PD due to SNCA mutations and demonstrated brain-region specific alterations of α-synuclein multimers in sporadic PD patients following the classical Braak spreading theory. In this study, we assessed relative levels of disordered and higher-ordered multimeric forms of cytosolic α-synuclein in blood from familial PD with G51D mutations and sporadic PD patients. We used an adapted in vitro-cross-linking protocol for human EDTA-whole blood. The relative levels of higher-ordered α-synuclein tetramers were diminished in blood from familial PD and sporadic PD patients compared to controls. Interestingly, the relative amount of α-synuclein tetramers was already decreased in asymptomatic G51D carriers, supporting the hypothesis that α-synuclein multimer destabilization precedes the development of clinical PD. Our data, therefore suggest that measuring α-synuclein tetramers in blood may have potential as a facile biomarker assay for early detection and quantitative tracking of PD progression.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Parkinson / Alfa-Sinucleína Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: EMBO Mol Med Asunto de la revista: BIOLOGIA MOLECULAR Año: 2024 Tipo del documento: Article Pais de publicación: Alemania

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Parkinson / Alfa-Sinucleína Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: EMBO Mol Med Asunto de la revista: BIOLOGIA MOLECULAR Año: 2024 Tipo del documento: Article Pais de publicación: Alemania