ArticleNature medicine2024
Plasma extracellular vesicle tau and TDP-43 as diagnostic biomarkers in FTD and ALS.
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Article in Nature medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 137 papers, 3 of them syntheses that pooled it.
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137citing papers in PubMed, 3 pooled it
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Who cites it
137 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Extracellular vesicles as a liquid biopsy for amyotrophic lateral sclerosis: a systematic review and meta-analysis.Journal of translational medicine · 2026Pooled it
- Diagnostic and Prognostic Value of Blood and Cerebrospinal Fluid Biomarkers in Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis.European journal of neurology · 2025Pooled it
- Efficacy and safety of pharmacological and biological therapies for amyotrophic lateral sclerosis: a network meta-analysis.Frontiers in neurologyPooled it
- Breaking barriers in peritoneal fibrosis: extracellular vesicles as promising diagnostic and therapeutic strategy.Annals of medicine · 2026Review
- Comparative Analysis of Plasma Biomarkers of Alzheimer's Disease and Frontotemporal Dementia: The Dual Role of Soluble Fractalkine as a Biomarker of Frontotemporal Dementia and Its Neuroprotective Effects in Cortical Neurons "In Vitro".Life (Basel, Switzerland) · 2026Article
- Peripheral TDP-43 pathology in amyotrophic lateral sclerosis: toward a systemic proteinopathy.Acta neuropathologica · 2026Review
- Significance of NAD anabolism profiles in neurological diseases.Metabolic brain disease · 2026Review
- Review
- Prion-like Protein TDP-43: Mechanisms, Diagnosis, and Therapeutic Prospects.Pathogens (Basel, Switzerland) · 2026Review
- Therapeutic Effects of miR-29b-Enriched Nanovesicles on Mitochondrial Injury and Neuroinflammatory Processes in Alzheimer's Disease.Neurotoxicity research · 2026Article
- Distinct proteomic CSF profiles in genetic frontotemporal lobar degeneration.Brain : a journal of neurology · 2026Article
- Comparison of TDP-43, NfL, and GFAP in cerebrospinal fluid and serum in Alzheimer's disease.European archives of psychiatry and clinical neuroscience · 2026Article
- Proteomic comparison of human neural cell-derived extracellular vesicles and parental cells from Alzheimer's disease and cognitively normal individuals.Science China. Life sciences · 2026Article
- Methodological insights and clinical outcomes in ALS and FTLD: lessons from the SPIN cohort.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- TDP-43 proteinopathy as a biomarker and therapeutic target in amyotrophic lateral sclerosis.Biochemical Society transactions · 2026Review
- The New Spine of Access to the Brain's Secrets: Extracellular Vesicles from Cerebrospinal Fluid Liquid Biopsies in CNS Diseases and Blood-Brain Barrier Research.Molecular neurobiology · 2026Review
- Alzheimer's Disease Co-Pathology and Cognitive Impairment in Amyotrophic Lateral Sclerosis.Annals of neurology · 2026Article
- Brain targeting and trafficking of extracellular vesicles in central nervous system diseases: a therapeutic roadmap.Nanomedicine (London, England) · 2026Review
- Frontotemporal dementia associated CHCHD10Cell death & disease · 2026Article
- An acetylated Tau-174 CSF biomarker discriminates between TDP-43 and tau pathology in patients with frontotemporal lobar degeneration.Nature medicine · 2026Article
77 more citing papers are in PubMed but not listed here.
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Authors and funding
85 authors.
Madhurima Chatterjee *German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Selcuk Özdemir *German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Christian FritzGerman Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Wiebke MöbiusDepartment of Neurogenetics, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.ORCID 0000-0002-2902-7165
Luca KleineidamGerman Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Eckhard MandelkowDepartment of Old Age Psychiatry and Cognitive Disorders, University Hospital Bonn, University of Bonn, Bonn, Germany.ORCID 0000-0003-4655-4829
Jacek BiernatDepartment of Old Age Psychiatry and Cognitive Disorders, University Hospital Bonn, University of Bonn, Bonn, Germany.
Cem DoğduGerman Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Oliver PetersGerman Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.
Nicoleta Carmen CosmaGerman Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.ORCID 0000-0002-2656-8046
Xiao WangGerman Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.
Luisa-Sophia SchneiderGerman Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.
Josef PrillerGerman Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.ORCID 0000-0001-7596-0979
Eike SpruthDepartment of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Andrea A KühnGerman Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.ORCID 0000-0002-4134-9060
Patricia KrauseMovement Disorder and Neuromodulation Unit, Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Thomas KlockgetherGerman Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Ina R VogtGerman Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Okka KimmichGerman Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Annika SpottkeGerman Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Daniel C HoffmannGerman Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Klaus FliessbachGerman Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Carolin MiklitzGerman Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Cornelia McCormickGerman Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Patrick WeydtGerman Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Björn FalkenburgerGerman Center for Neurodegenerative Diseases (DZNE), Dresden, Germany.
Moritz BrandtGerman Center for Neurodegenerative Diseases (DZNE), Dresden, Germany.
René GuentherGerman Center for Neurodegenerative Diseases (DZNE), Dresden, Germany.
Elisabeth DinterGerman Center for Neurodegenerative Diseases (DZNE), Dresden, Germany.
Jens WiltfangGerman Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
Niels HansenGerman Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
Mathias BährGerman Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
Inga ZerrGerman Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
Agnes FlöelDepartment of Neurology, University Medicine Greifswald, Greifswald, Germany.
Peter J NestorGerman Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.
Emrah DüzelGerman Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.
Wenzel GlanzGerman Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.
Enise IncesoyGerman Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.
Katharina BürgerGerman Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
Daniel JanowitzInstitute for Stroke and Dementia Research, University Hospital, LMU Munich, Munich, Germany.
Robert PerneczkyGerman Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
Boris S RauchmannDepartment of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany.
Franziska HopfnerDepartment of Neurology, University Hospital of Munich, Ludwig-Maximilians-Universität (LMU) Munich, Munich, Germany.
Olivia WagemannGerman Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
Johannes LevinGerman Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
Stefan TeipelGerman Centre for Neurodegenerative Diseases (DZNE), Rostock/Greifswald, Germany.
Ingo KilimannGerman Centre for Neurodegenerative Diseases (DZNE), Rostock/Greifswald, Germany.
Doreen GoerssGerman Centre for Neurodegenerative Diseases (DZNE), Rostock/Greifswald, Germany.
Johannes PrudloGerman Centre for Neurodegenerative Diseases (DZNE), Rostock/Greifswald, Germany.
Thomas GasserGerman Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
Kathrin BrockmannGerman Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.ORCID 0000-0002-7515-8596
David MengelGerman Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
Milan ZimmermannGerman Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
Matthis SynofzikGerman Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
Carlo WilkeGerman Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
Judit Selma-GonzálezSant Pau Memory Unit, Department of Neurology, Institut de Recerca Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
Janina Turon-SansMotor Neuron Disease Clinic, Neuromuscular Diseases Unit, Institut de Recerca Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
Miguel Angel Santos-SantosSant Pau Memory Unit, Department of Neurology, Institut de Recerca Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
Daniel AlcoleaSant Pau Memory Unit, Department of Neurology, Institut de Recerca Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.ORCID 0000-0002-3819-3245
Sara Rubio-GuerraSant Pau Memory Unit, Department of Neurology, Institut de Recerca Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.ORCID 0000-0001-7652-8029
Juan ForteaSant Pau Memory Unit, Department of Neurology, Institut de Recerca Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.ORCID 0000-0002-1340-638X
Álvaro CarbayoMotor Neuron Disease Clinic, Neuromuscular Diseases Unit, Institut de Recerca Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.ORCID 0000-0001-9282-8603
Alberto LleóSant Pau Memory Unit, Department of Neurology, Institut de Recerca Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.ORCID 0000-0002-2568-5478
Ricardo Rojas-GarcíaMotor Neuron Disease Clinic, Neuromuscular Diseases Unit, Institut de Recerca Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
Ignacio Illán-GalaSant Pau Memory Unit, Department of Neurology, Institut de Recerca Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
Michael WagnerGerman Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Ingo FrommannGerman Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.ORCID 0000-0002-7244-2014
Sandra RoeskeGerman Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.ORCID 0000-0002-8262-4356
Lucas BertramGerman Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.ORCID 0009-0005-3594-6925
Michael T HenekaLuxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Belvaux, Luxembourg.ORCID 0000-0003-4996-1630
Frederic BrosseronGerman Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Alfredo RamirezGerman Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.ORCID 0000-0003-4991-763X
Matthias SchmidGerman Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Rudi BeschornerGerman Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.ORCID 0000-0003-1109-915X
Annett HalleGerman Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Jochen HermsGerman Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
Manuela NeumannGerman Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
Nicolas R BarthélemyDepartment of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
Randall J BatemanDepartment of Neurology, Washington University School of Medicine, St. Louis, MO, USA.ORCID 0000-0002-7729-1702
Patrizia RizzuGerman Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
Peter HeutinkGerman Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
Oriol Dols-IcardoSant Pau Memory Unit, Department of Neurology, Institut de Recerca Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.ORCID 0000-0003-2656-8748
Günter HöglingerGerman Center for Neurodegenerative Diseases (DZNE), Munich, Germany.ORCID 0000-0001-7587-6187
Andreas HermannGerman Centre for Neurodegenerative Diseases (DZNE), Rostock/Greifswald, Germany.ORCID 0000-0002-7364-7791
Anja SchneiderGerman Center for Neurodegenerative Diseases (DZNE), Bonn, Germany. anja.schneider@dzne.de.ORCID 0000-0001-9540-8700
Funding
Program Development and Pilot CoreP30AG066614 · NIA · UNIVERSITY OF TEXAS AT AUSTIN · PI DEBRA J. UMBERSON · 2020 to 2026
$5.2MBilingual Factors Associated with Cognitive Reserve and Linguistic Resilience in Hispanics with Primary Progressive AphasiaR01AG080470 · NIA · UNIVERSITY OF TEXAS AT AUSTIN · PI Stephanie M Grasso · 2023 to 2026
$2.8MNIA NIH HHS P30 AG066614NIA NIH HHS R01 AG080470
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 >0.9, and between TDP-43 and tau pathology in bvFTD. Both markers strongly correlated with neurodegeneration, and clinical and neuropsychological markers of disease severity. Findings were replicated in an independent validation cohort of 292 patients including 34 genetically confirmed cases. Taken together, the combination of EV TDP-43 levels and EV 3R/4R tau ratios may aid the molecular diagnosis of FTD, FTD spectrum disorders and ALS, providing a potential biomarker to monitor disease progression and target engagement in clinical trials.
Indexed as
Amyotrophic Lateral SclerosisBiomarkersDNA-Binding ProteinsExtracellular VesiclesFrontotemporal Dementiatau ProteinsAgedFemaleHumansMaleMiddle AgedProtein IsoformsSupranuclear Palsy, ProgressiveBiomarkersDNA-Binding ProteinsMAPT protein, humanProtein IsoformsTARDBP protein, humantau Proteins
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