Plasma extracellular vesicle tau and TDP-43 as diagnostic biomarkers in FTD and ALS
Chatterjee, Madhurima (German Center for Neurodegenerative Diseases (DZNE))
Özdemir, Selcuk (Atatürk University)
Fritz, Christian (German Center for Neurodegenerative Diseases (DZNE))
Möbius, Wiebke (University of Göttingen)
Kleineidam, Luca (University of Bonn)
Mandelkow, Eckhard (University of Bonn)
Biernat, Jacek (University of Bonn)
Doğdu, Cem (German Center for Neurodegenerative Diseases (DZNE))
Peters, Oliver (Charité-Universitätsmedizin Berlin)
Cosma, Nicoleta Carmen (German Center for Neurodegenerative Diseases (DZNE))
Wang, Xiao (German Center for Neurodegenerative Diseases (DZNE))
Schneider, Luisa-Sophia (German Center for Neurodegenerative Diseases (DZNE))
Priller, Josef (University of Edinburgh and UK DRI)
Spruth, Eike (Charité-Universitätsmedizin Berlin)
Kühn, Andrea A. (Charité-Universitätsmedizin Berlin)
Krause, Patricia (Charité-Universitätsmedizin Berlin)
Klockgether, Thomas (University of Bonn)
Vogt, Ina R. (German Center for Neurodegenerative Diseases (DZNE))
Kimmich, Okka (German Center for Neurodegenerative Diseases (DZNE))
Spottke, Annika (Department of Neurology. University of Bonn)
Hoffmann, Daniel C. (German Center for Neurodegenerative Diseases (DZNE))
Fliessbach, Klaus (University of Bonn)
Miklitz, Carolin (University of Bonn)
McCormick, Cornelia (University of Bonn)
Weydt, Patrick (German Center for Neurodegenerative Diseases (DZNE))
Falkenburger, Björn (Technische Universität Dresden)
Brandt, Moritz (Technische Universität Dresden)
Guenther, René (Technische Universität Dresden)
Dinter, Elisabeth (Technische Universität Dresden)
Wiltfang, Jens (Universidade de Aveiro)
Hansen, Niels (University of Göttingen)
Bähr, Mathias (University Medical Center Göttingen)
Zerr, Inga (Georg August University)
Flöel, Agnes (German Centre for Neurodegenerative Diseases (Bonn, Alemanya))
Nestor, Peter J. (University of Queensland and Mater Public Hospital)
Düzel, Emrah (University College London)
Glanz, Wenzel (University Hospital Magdeburg)
Incesoy, Enise (University Hospital Magdeburg)
Bürger, Katharina (University Hospital. LMU Munich)
Janowitz, Daniel (University Hospital. LMU Munich)
Perneczky, Robert (Imperial College London)
Rauchmann, Boris S. (University of Sheffield)
Hopfner, Franziska (University Hospital of Munich)
Wagemann, Olivia (University Hospital of Munich)
Levin, Johannes (University Hospital of Munich)
Teipel, Stefan (Rostock University Medical Center)
Kilimann, Ingo (Rostock University Medical Center)
Goerss, Doreen (German Centre for Neurodegenerative Diseases (Bonn, Alemanya))
Prudlo, Johannes (Rostock University Medical Centre)
Gasser, Thomas (University of Tübingen)
Brockmann, Kathrin (University of Tübingen)
Mengel, David (University of Tübingen)
Zimmermann, Milan (University of Tübingen)
Synofzik, Matthis (University of Tübingen)
Wilke, Carlo (University of Tübingen)
Selma Gonzalez, Judit (Institut de Recerca Sant Pau)
Turon-Sans, Janina (Institut de Recerca Sant Pau)
Santos Santos, Miguel Ángel (Institut de Recerca Sant Pau)
Alcolea, Daniel (Institut de Recerca Sant Pau)
Rubio Guerra, Sara (Institut de Recerca Sant Pau)
Fortea, Juan (Institut de Recerca Sant Pau)
Carbayo Viejo, Álvaro (Institut de Recerca Sant Pau)
Lleó, Alberto (Institut de Recerca Sant Pau)
Rojas-Garcia, Ricardo (Institut de Recerca Sant Pau)
Illán-Gala, Ignacio (Institut de Recerca Sant Pau)
Wagner, Michael (University of Bonn)
Frommann, Ingo (University of Bonn)
Roeske, Sandra (German Center for Neurodegenerative Diseases (DZNE))
Bertram, Lucas (German Center for Neurodegenerative Diseases (DZNE))
Heneka, Michael (University of Massachussetss Medical School)
Brosseron, Frederic (German Center for Neurodegenerative Diseases (DZNE))
Ramirez, Alfredo (University of Texas Health Science Center at San Antonio)
Schmid, Matthias (University Hospital Bonn (Bonn, Alemanya))
Beschorner, Rudi (University of Tübingen)
Halle, Annett (University Hospital Bonn (Bonn, Alemanya))
Herms, Jochen (Ludwig-Maximilians-University Munich)
Neumann, Manuela (University of Tübingen)
Barthélemy, Nicolas R. (Tracy Family SILQ Center for Neurodegenerative Biology)
Bateman, Randall (Tracy Family SILQ Center for Neurodegenerative Biology)
Rizzu, Patrizia (German Center for Neurodegenerative Diseases (DZNE))
Heutink, Peter (German Center for Neurodegenerative Diseases (DZNE))
Dols Icardo, Oriol (Institut de Recerca Sant Pau)
Höglinger, Günter (University Hospital of Munich)
Hermann, Andreas (University Medical Center Rostock)
Schneider, Anja (University of Bonn)
Universitat Autònoma de Barcelona

Date:	2024
Abstract:	Minimally invasive biomarkers are urgently needed to detect molecular pathology in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Here, we show that plasma extracellular vesicles (EVs) contain quantifiable amounts of TDP-43 and full-length tau, which allow the quantification of 3-repeat (3R) and 4-repeat (4R) tau isoforms. Plasma EV TDP-43 levels and EV 3R/4R tau ratios were determined in a cohort of 704 patients, including 37 genetically and 31 neuropathologically proven cases. Diagnostic groups comprised patients with TDP-43 proteinopathy ALS, 4R tauopathy progressive supranuclear palsy, behavior variant FTD (bvFTD) as a group with either tau or TDP-43 pathology, and healthy controls. EV tau ratios were low in progressive supranuclear palsy and high in bvFTD with tau pathology. EV TDP-43 levels were high in ALS and in bvFTD with TDP-43 pathology. Both markers discriminated between the diagnostic groups with area under the curve values.
Grants:	Instituto de Salud Carlos III PI19/00882 Instituto de Salud Carlos III PI18/00435 Instituto de Salud Carlos III PI22/00611 Instituto de Salud Carlos III PI21/00791 Instituto de Salud Carlos III PI18/00326 Instituto de Salud Carlos III PI21/01395
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Diagnostic markers ; Neurological disorders
Published in:	Nature Medicine, Vol. 30 Núm. 6 (june 2024) , p. 1771-1783, ISSN 1546-170X

DOI: 10.1038/s41591-024-02937-4
PMID: 38890531

34 p, 11.8 MB

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