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

Elodie Leroux; Romain Perbet; Raphaëlle Caillierez; Kevin Richetin; Sarah Lieger; Jeanne Espourteille; Thomas Bouillet; Séverine Bégard; Clément Danis; Anne Loyens; Nicolas Toni; Nicole Déglon; Vincent Deramecourt; Susanna Schraen-Maschke; Luc Buée; Morvane Colin

doi:10.1016/j.ymthe.2021.09.020

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

Mol Ther. 2022 Feb 2;30(2):782-797. doi: 10.1016/j.ymthe.2021.09.020. Epub 2021 Sep 24.

Authors

Elodie Leroux¹, Romain Perbet¹, Raphaëlle Caillierez¹, Kevin Richetin², Sarah Lieger¹, Jeanne Espourteille³, Thomas Bouillet¹, Séverine Bégard¹, Clément Danis¹, Anne Loyens¹, Nicolas Toni³, Nicole Déglon⁴, Vincent Deramecourt¹, Susanna Schraen-Maschke¹, Luc Buée⁵, Morvane Colin⁶

Affiliations

¹ Université de Lille, INSERM, CHU-Lille, Lille Neuroscience & Cognition, 59000 Lille, France.
² Department of Psychiatry, Center for Psychiatric Neurosciences, Lausanne University Hospital (CHUV) and University of Lausanne, 1011 Lausanne, Switzerland; Lausanne University Hospital (CHUV) and University of Lausanne, Neuroscience Research Center (CRN), Laboratory of Cellular and Molecular Neurotherapies, 1011 Lausanne, Switzerland; Lausanne University Hospital (CHUV) and University of Lausanne, Department of Clinical Neuroscience (DNC), Laboratory of Cellular and Molecular Neurotherapies, 1011 Lausanne, Switzerland.
³ Department of Psychiatry, Center for Psychiatric Neurosciences, Lausanne University Hospital (CHUV) and University of Lausanne, 1011 Lausanne, Switzerland.
⁴ Lausanne University Hospital (CHUV) and University of Lausanne, Neuroscience Research Center (CRN), Laboratory of Cellular and Molecular Neurotherapies, 1011 Lausanne, Switzerland; Lausanne University Hospital (CHUV) and University of Lausanne, Department of Clinical Neuroscience (DNC), Laboratory of Cellular and Molecular Neurotherapies, 1011 Lausanne, Switzerland.
⁵ Université de Lille, INSERM, CHU-Lille, Lille Neuroscience & Cognition, 59000 Lille, France. Electronic address: [email protected].
⁶ Université de Lille, INSERM, CHU-Lille, Lille Neuroscience & Cognition, 59000 Lille, France. Electronic address: [email protected].

Abstract

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.

Keywords: Alzheimer’s disease; biological fluids; exosomes; microvesicles; prion-like propagation; seeding; tauopathies.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease* / genetics
Alzheimer Disease* / pathology
Brain / metabolism
Extracellular Vesicles* / metabolism
Humans
Tauopathies* / genetics
Tauopathies* / pathology
tau Proteins / genetics
tau Proteins / metabolism

Substances

tau Proteins