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Extracellular vesicles: Major actors of heterogeneity in tau spreading among human tauopathies

Tauopathies are neurodegenerative diseases characterized by tau inclusions in brain cells. Seed-competent tau species have been suggested to spread from cell to cell in a stereotypical manner, indicating that this may involve a prion-like mechanism. Although the intercellular mechanisms of transfer...

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Autores principales: Leroux, Elodie, Perbet, Romain, Caillierez, Raphaëlle, Richetin, Kevin, Lieger, Sarah, Espourteille, Jeanne, Bouillet, Thomas, Bégard, Séverine, Danis, Clément, Loyens, Anne, Toni, Nicolas, Déglon, Nicole, Deramecourt, Vincent, Schraen-Maschke, Susanna, Buée, Luc, Colin, Morvane
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8821971/
https://www.ncbi.nlm.nih.gov/pubmed/34563677
http://dx.doi.org/10.1016/j.ymthe.2021.09.020
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author Leroux, Elodie
Perbet, Romain
Caillierez, Raphaëlle
Richetin, Kevin
Lieger, Sarah
Espourteille, Jeanne
Bouillet, Thomas
Bégard, Séverine
Danis, Clément
Loyens, Anne
Toni, Nicolas
Déglon, Nicole
Deramecourt, Vincent
Schraen-Maschke, Susanna
Buée, Luc
Colin, Morvane
author_facet Leroux, Elodie
Perbet, Romain
Caillierez, Raphaëlle
Richetin, Kevin
Lieger, Sarah
Espourteille, Jeanne
Bouillet, Thomas
Bégard, Séverine
Danis, Clément
Loyens, Anne
Toni, Nicolas
Déglon, Nicole
Deramecourt, Vincent
Schraen-Maschke, Susanna
Buée, Luc
Colin, Morvane
author_sort Leroux, Elodie
collection PubMed
description Tauopathies are neurodegenerative diseases characterized by tau inclusions in brain cells. Seed-competent tau species have been suggested to spread from cell to cell in a stereotypical manner, indicating that this may involve a prion-like mechanism. Although the intercellular mechanisms of transfer are unclear, extracellular vesicles (EVs) could be potential shuttles. We assessed this in humans by preparing vesicles from fluids (brain-derived enriched EVs [BD-EVs]). These latter were isolated from different brain regions in various tauopathies, and their seeding potential was assessed in vitro and in vivo. We observed considerable heterogeneity among tauopathies and brain regions. The most striking evidence was coming mainly from Alzheimer’s disease where the BD-EVs clearly contain pathological species that can induce tau lesions in vivo. The results support the hypothesis that BD-EVs participate in the prion-like propagation of tau pathology among tauopathies, and there may be implications for diagnostic and therapeutic strategies.
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spelling pubmed-88219712023-02-02 Extracellular vesicles: Major actors of heterogeneity in tau spreading among human tauopathies Leroux, Elodie Perbet, Romain Caillierez, Raphaëlle Richetin, Kevin Lieger, Sarah Espourteille, Jeanne Bouillet, Thomas Bégard, Séverine Danis, Clément Loyens, Anne Toni, Nicolas Déglon, Nicole Deramecourt, Vincent Schraen-Maschke, Susanna Buée, Luc Colin, Morvane Mol Ther Original Article Tauopathies are neurodegenerative diseases characterized by tau inclusions in brain cells. Seed-competent tau species have been suggested to spread from cell to cell in a stereotypical manner, indicating that this may involve a prion-like mechanism. Although the intercellular mechanisms of transfer are unclear, extracellular vesicles (EVs) could be potential shuttles. We assessed this in humans by preparing vesicles from fluids (brain-derived enriched EVs [BD-EVs]). These latter were isolated from different brain regions in various tauopathies, and their seeding potential was assessed in vitro and in vivo. We observed considerable heterogeneity among tauopathies and brain regions. The most striking evidence was coming mainly from Alzheimer’s disease where the BD-EVs clearly contain pathological species that can induce tau lesions in vivo. The results support the hypothesis that BD-EVs participate in the prion-like propagation of tau pathology among tauopathies, and there may be implications for diagnostic and therapeutic strategies. American Society of Gene & Cell Therapy 2022-02-02 2021-09-24 /pmc/articles/PMC8821971/ /pubmed/34563677 http://dx.doi.org/10.1016/j.ymthe.2021.09.020 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Leroux, Elodie
Perbet, Romain
Caillierez, Raphaëlle
Richetin, Kevin
Lieger, Sarah
Espourteille, Jeanne
Bouillet, Thomas
Bégard, Séverine
Danis, Clément
Loyens, Anne
Toni, Nicolas
Déglon, Nicole
Deramecourt, Vincent
Schraen-Maschke, Susanna
Buée, Luc
Colin, Morvane
Extracellular vesicles: Major actors of heterogeneity in tau spreading among human tauopathies
title Extracellular vesicles: Major actors of heterogeneity in tau spreading among human tauopathies
title_full Extracellular vesicles: Major actors of heterogeneity in tau spreading among human tauopathies
title_fullStr Extracellular vesicles: Major actors of heterogeneity in tau spreading among human tauopathies
title_full_unstemmed Extracellular vesicles: Major actors of heterogeneity in tau spreading among human tauopathies
title_short Extracellular vesicles: Major actors of heterogeneity in tau spreading among human tauopathies
title_sort extracellular vesicles: major actors of heterogeneity in tau spreading among human tauopathies
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8821971/
https://www.ncbi.nlm.nih.gov/pubmed/34563677
http://dx.doi.org/10.1016/j.ymthe.2021.09.020
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