Home > Publications Database > Plasma extracellular vesicle tau and TDP-43 as diagnostic biomarkers in FTD and ALS. > print

001     270411
005     20240826165955.0
024 7 _ |a 10.1038/s41591-024-02937-4
|2 doi
024 7 _ |a pmid:38890531
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024 7 _ |a pmc:PMC11186765
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024 7 _ |a 1078-8956
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024 7 _ |a 1546-170X
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024 7 _ |a altmetric:164636141
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037 _ _ |a DZNE-2024-00791
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Chatterjee, Madhurima
|0 P:(DE-2719)2812856
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245 _ _ |a Plasma extracellular vesicle tau and TDP-43 as diagnostic biomarkers in FTD and ALS.
260 _ _ |a New York, NY
|c 2024
|b Nature America Inc.
336 7 _ |a article
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336 7 _ |a Output Types/Journal article
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336 7 _ |a Journal Article
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336 7 _ |a ARTICLE
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336 7 _ |a JOURNAL_ARTICLE
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336 7 _ |a Journal Article
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520 _ _ |a 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.
536 _ _ |a 353 - Clinical and Health Care Research (POF4-353)
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536 _ _ |a 354 - Disease Prevention and Healthy Aging (POF4-354)
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536 _ _ |a 352 - Disease Mechanisms (POF4-352)
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588 _ _ |a Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
650 _ 7 |a tau Proteins
|2 NLM Chemicals
650 _ 7 |a Biomarkers
|2 NLM Chemicals
650 _ 7 |a DNA-Binding Proteins
|2 NLM Chemicals
650 _ 7 |a TARDBP protein, human
|2 NLM Chemicals
650 _ 7 |a MAPT protein, human
|2 NLM Chemicals
650 _ 7 |a Protein Isoforms
|2 NLM Chemicals
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Amyotrophic Lateral Sclerosis: blood
|2 MeSH
650 _ 2 |a Amyotrophic Lateral Sclerosis: diagnosis
|2 MeSH
650 _ 2 |a Amyotrophic Lateral Sclerosis: pathology
|2 MeSH
650 _ 2 |a Amyotrophic Lateral Sclerosis: genetics
|2 MeSH
650 _ 2 |a tau Proteins: blood
|2 MeSH
650 _ 2 |a tau Proteins: metabolism
|2 MeSH
650 _ 2 |a Extracellular Vesicles: metabolism
|2 MeSH
650 _ 2 |a Frontotemporal Dementia: blood
|2 MeSH
650 _ 2 |a Frontotemporal Dementia: diagnosis
|2 MeSH
650 _ 2 |a Frontotemporal Dementia: genetics
|2 MeSH
650 _ 2 |a Frontotemporal Dementia: pathology
|2 MeSH
650 _ 2 |a Biomarkers: blood
|2 MeSH
650 _ 2 |a DNA-Binding Proteins: blood
|2 MeSH
650 _ 2 |a DNA-Binding Proteins: genetics
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Aged
|2 MeSH
650 _ 2 |a Middle Aged
|2 MeSH
650 _ 2 |a Supranuclear Palsy, Progressive: blood
|2 MeSH
650 _ 2 |a Supranuclear Palsy, Progressive: diagnosis
|2 MeSH
650 _ 2 |a Protein Isoforms: blood
|2 MeSH
700 1 _ |a Oezdemir, Selcuk
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700 1 _ |a Fritz, Christian
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773 _ _ |a 10.1038/s41591-024-02937-4
|g Vol. 30, no. 6, p. 1771 - 1783
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|t Nature medicine
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Marc 21