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@ARTICLE{Chatterjee:270411,
author = {Chatterjee, Madhurima and Oezdemir, Selcuk and Fritz,
Christian and Möbius, Wiebke and Kleineidam, Luca and
Mandelkow, Eckhard and Biernat, Jacek and Doğdu, Cem and
Peters, Oliver and Cosma, Nicoleta-Carmen and Wang, Xiao and
Schneider, Luisa-Sophia and Priller, Josef and Spruth, Eike
and Kühn, Andrea A and Krause, Patricia and Klockgether,
Thomas and Vogt, Ina R and Kimmich, Okka and Spottke, Annika
and Hoffmann, Daniel C and Fliessbach, Klaus and Miklitz,
Carolin and McCormick, Cornelia and Weydt, Patrick and
Falkenburger, Björn and Brandt, Moritz and Guenther, René
and Dinter, Elisabeth and Wiltfang, Jens and Hansen, Niels
and Bähr, Mathias and Zerr, Inga and Flöel, Agnes and
Nestor, Peter John and Düzel, Emrah and Glanz, Wenzel and
Incesoy, Enise and Bürger, Katharina and Janowitz, Daniel
and Perneczky, Robert and Rauchmann, Boris Stephan and
Hopfner, Franziska and Wagemann, Olivia and Levin, Johannes
and Teipel, Stefan and Kilimann, Ingo and Goerss, Doreen and
Prudlo, Johannes and Gasser, Thomas and Brockmann, Kathrin
and Mengel, David and Zimmermann, Milan and Synofzik,
Matthis and Wilke, Carlo and Selma-González, Judit and
Turon-Sans, Janina and Santos-Santos, Miguel Angel and
Alcolea, Daniel and Rubio-Guerra, Sara and Fortea, Juan and
Carbayo, Álvaro and Lleó, Alberto and Rojas-García,
Ricardo and Illán-Gala, Ignacio and Wagner, Michael and
Frommann, Ingo and Röske, Sandra and Bertram, Lucas and
Heneka, Michael T and Brosseron, Frederic and Ramirez,
Alfredo and Schmid, Matthias and Beschorner, Rudi and Halle,
Annett and Herms, Jochen and Neumann, Manuela and
Barthélemy, Nicolas R and Bateman, Randall J and Rizzu,
Patrizia and Heutink, Peter and Dols-Icardo, Oriol and
Höglinger, Günter and Hermann, Andreas and Schneider,
Anja},
title = {{P}lasma extracellular vesicle tau and {TDP}-43 as
diagnostic biomarkers in {FTD} and {ALS}.},
journal = {Nature medicine},
volume = {30},
number = {6},
issn = {1078-8956},
address = {New York, NY},
publisher = {Nature America Inc.},
reportid = {DZNE-2024-00791},
pages = {1771 - 1783},
year = {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 >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.},
keywords = {Humans / Amyotrophic Lateral Sclerosis: blood / Amyotrophic
Lateral Sclerosis: diagnosis / Amyotrophic Lateral
Sclerosis: pathology / Amyotrophic Lateral Sclerosis:
genetics / tau Proteins: blood / tau Proteins: metabolism /
Extracellular Vesicles: metabolism / Frontotemporal
Dementia: blood / Frontotemporal Dementia: diagnosis /
Frontotemporal Dementia: genetics / Frontotemporal Dementia:
pathology / Biomarkers: blood / DNA-Binding Proteins: blood
/ DNA-Binding Proteins: genetics / Female / Male / Aged /
Middle Aged / Supranuclear Palsy, Progressive: blood /
Supranuclear Palsy, Progressive: diagnosis / Protein
Isoforms: blood / tau Proteins (NLM Chemicals) / Biomarkers
(NLM Chemicals) / DNA-Binding Proteins (NLM Chemicals) /
TARDBP protein, human (NLM Chemicals) / MAPT protein, human
(NLM Chemicals) / Protein Isoforms (NLM Chemicals)},
cin = {AG Schneider / AG Wagner / AG Klockgether / AG Spottke / AG
Hermann / Clinical Research (Munich) / AG Peters / AG
Priller / AG Dirnagl / AG Kühn / Patient Studies Bonn / AG
Falkenburger / AG Wiltfang / Clinical Dementia Research
(Göttingen) / AG Zerr / AG Flöel / AG Düzel / AG Dichgans
/ AG Teipel / AG Levin / AG Gasser / AG Heneka / AG Schmid
Bonn / AG Halle / AG Herms / AG Neumann / AG Rizzu},
ddc = {610},
cid = {I:(DE-2719)1011305 / I:(DE-2719)1011201 /
I:(DE-2719)1011001 / I:(DE-2719)1011103 / I:(DE-2719)1511100
/ I:(DE-2719)1111015 / I:(DE-2719)5000000 /
I:(DE-2719)5000007 / I:(DE-2719)1810002 / I:(DE-2719)5000008
/ I:(DE-2719)1011101 / I:(DE-2719)1710012 /
I:(DE-2719)1410006 / I:(DE-2719)1440015 /
I:(DE-2719)1440011-1 / I:(DE-2719)5000081 /
I:(DE-2719)5000006 / I:(DE-2719)5000022 / I:(DE-2719)1510100
/ I:(DE-2719)1111016 / I:(DE-2719)1210000 /
I:(DE-2719)1011303 / I:(DE-2719)1013028 / I:(DE-2719)1013034
/ I:(DE-2719)1110001 / I:(DE-2719)1210003 /
I:(DE-2719)1210009},
pnm = {353 - Clinical and Health Care Research (POF4-353) / 354 -
Disease Prevention and Healthy Aging (POF4-354) / 352 -
Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-353 / G:(DE-HGF)POF4-354 /
G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:38890531},
pmc = {pmc:PMC11186765},
doi = {10.1038/s41591-024-02937-4},
url = {https://pub.dzne.de/record/270411},
}
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