Extracellular vesicles: Major actors of heterogeneity in tau spreading among human tauopathies.
Alzheimer’s disease
biological fluids
exosomes
microvesicles
prion-like propagation
seeding
tauopathies
Journal
Molecular therapy : the journal of the American Society of Gene Therapy
ISSN: 1525-0024
Titre abrégé: Mol Ther
Pays: United States
ID NLM: 100890581
Informations de publication
Date de publication:
02 02 2022
02 02 2022
Historique:
received:
15
03
2021
revised:
12
07
2021
accepted:
20
09
2021
pubmed:
27
9
2021
medline:
8
4
2022
entrez:
26
9
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34563677
pii: S1525-0016(21)00475-5
doi: 10.1016/j.ymthe.2021.09.020
pmc: PMC8821971
pii:
doi:
Substances chimiques
tau Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
782-797Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
Références
J Biol Chem. 2008 Nov 14;283(46):32066-76
pubmed: 18725412
J Biol Chem. 2012 Feb 3;287(6):3842-9
pubmed: 22057275
J Alzheimers Dis. 2012;31(4):741-9
pubmed: 22699846
J Alzheimers Dis. 2019;67(2):541-553
pubmed: 30584143
J Neurochem. 2006 Oct;99(1):154-64
pubmed: 16987243
Nat Methods. 2016 Sep;13(9):731-40
pubmed: 27348712
Alzheimers Dement. 2019 Aug;15(8):1071-1080
pubmed: 31422798
Trends Cell Biol. 2017 Mar;27(3):172-188
pubmed: 27979573
Acta Neuropathol. 2021 Feb;141(2):235-256
pubmed: 33417012
Neuron. 2016 Nov 23;92(4):796-812
pubmed: 27974162
Acta Neuropathol Commun. 2017 Nov 29;5(1):91
pubmed: 29187252
Proc Natl Acad Sci U S A. 2014 Oct 14;111(41):E4376-85
pubmed: 25261551
Nature. 2017 Jul 13;547(7662):185-190
pubmed: 28678775
Brain. 2021 Feb 12;144(1):288-309
pubmed: 33246331
Brain. 2018 Feb 1;141(2):521-534
pubmed: 29253099
Int J Mol Sci. 2018 Feb 27;19(3):
pubmed: 29495441
Acta Neuropathol Commun. 2018 Nov 29;6(1):132
pubmed: 30497516
Acta Neuropathol. 1991;82(4):239-59
pubmed: 1759558
Nat Neurosci. 2020 Dec;23(12):1567-1579
pubmed: 33169029
Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10252-7
pubmed: 17535890
Brain. 2019 Jun 1;142(6):1736-1750
pubmed: 31038156
Acta Neuropathol. 1994;87(2):115-24
pubmed: 8171960
Neurobiol Aging. 2020 Feb;86:102-111
pubmed: 31883770
Cell Rep. 2018 Nov 20;25(8):2027-2035.e4
pubmed: 30463001
EMBO Rep. 2013 Apr;14(4):389-94
pubmed: 23412472
Front Neurosci. 2019 Jul 02;13:698
pubmed: 31312118
J Alzheimers Dis. 2020;73(3):1105-1123
pubmed: 31884489
Behav Neurol. 1998;11(4):211-216
pubmed: 11568422
Nat Med. 2020 Aug;26(8):1256-1263
pubmed: 32572268
Nat Cell Biol. 2012 Jun 03;14(7):677-85
pubmed: 22660413
Biochemistry. 1997 Jul 1;36(26):8114-24
pubmed: 9201960
J Neurosci Res. 1997 Apr 15;48(2):128-32
pubmed: 9130141
J Extracell Vesicles. 2014 Sep 08;3:
pubmed: 25279113
J Neurosci. 2002 Nov 1;22(21):9340-51
pubmed: 12417659
Ann Neurol. 2016 Feb;79(2):272-87
pubmed: 26583316
Nat Methods. 2014 Mar;11(3):319-24
pubmed: 24487582
PLoS One. 2017 May 26;12(5):e0178288
pubmed: 28552936
J Neurochem. 2017 May;141(4):592-605
pubmed: 28222213
Acta Neuropathol Commun. 2018 Feb 15;6(1):10
pubmed: 29448966
Proteins. 2016 Apr;84(4):427-34
pubmed: 26800003
Nat Biotechnol. 2008 Dec;26(12):1367-72
pubmed: 19029910
Neuron. 2014 Jun 18;82(6):1271-88
pubmed: 24857020
Mol Neurodegener. 2017 Jan 13;12(1):5
pubmed: 28086931
Acta Neuropathol Commun. 2019 Feb 15;7(1):22
pubmed: 30767766
Acta Neuropathol. 1996;91(4):351-9
pubmed: 8928611
PLoS One. 2019 Jan 22;14(1):e0210864
pubmed: 30668577
J Proteome Res. 2011 Apr 1;10(4):1794-805
pubmed: 21254760
Cell Rep. 2018 May 15;23(7):2039-2055
pubmed: 29768203
J Alzheimers Dis. 2019;70(3):667-680
pubmed: 31256134
Neurobiol Dis. 2017 Sep;105:74-83
pubmed: 28502805
Nat Rev Mol Cell Biol. 2018 Apr;19(4):213-228
pubmed: 29339798
Biomol Eng. 2001 Jun;17(6):157-65
pubmed: 11337275
Eur J Biochem. 1998 Mar 15;252(3):542-52
pubmed: 9546672
Brain. 2018 Feb 1;141(2):535-549
pubmed: 29253129
Acta Neuropathol. 2020 Jan;139(1):3-25
pubmed: 31686182
Cells. 2018 Nov 03;7(11):
pubmed: 30400277
Front Neurosci. 2017 May 22;11:278
pubmed: 28588440
Neuron. 2018 Mar 21;97(6):1284-1298.e7
pubmed: 29566794
Ann Neurol. 1998 Feb;43(2):193-204
pubmed: 9485060
J Biol Chem. 2016 Jun 10;291(24):12445-12466
pubmed: 27030011
Brain Res Brain Res Rev. 2000 Aug;33(1):95-130
pubmed: 10967355
Acta Neuropathol. 2018 Nov;136(5):699-708
pubmed: 30276465
Am J Pathol. 2006 Aug;169(2):599-616
pubmed: 16877359
J Alzheimers Dis. 2013;37(4):769-76
pubmed: 23948919
Brain. 1996 Aug;119 ( Pt 4):1123-36
pubmed: 8813277
J Neuropathol Exp Neurol. 2004 Sep;63(9):911-8
pubmed: 15453090
FEBS Lett. 1998 Aug 21;433(3):201-4
pubmed: 9744794
Biochim Biophys Acta. 2015 Jul;1853(7):1646-57
pubmed: 25791428
EMBO J. 2016 Jul 15;35(14):1537-49
pubmed: 27261198
J Extracell Vesicles. 2018 Nov 23;7(1):1535750
pubmed: 30637094
Brain. 2007 Jun;130(Pt 6):1566-76
pubmed: 17525140
Proc Natl Acad Sci U S A. 1975 May;72(5):1858-62
pubmed: 1057175
Front Neurosci. 2019 Jun 26;13:649
pubmed: 31293374
Sci Rep. 2019 May 8;9(1):7089
pubmed: 31068645
Nature. 2011 May 19;473(7347):337-42
pubmed: 21593866
Alzheimers Dement. 2015 Jun;11(6):600-7.e1
pubmed: 25130657
Alzheimers Dement. 2020 Jun;16(6):896-907
pubmed: 32301581
Nature. 2019 Apr;568(7752):420-423
pubmed: 30894745
Neurology. 1999 Apr 12;52(6):1158-65
pubmed: 10214737
Alzheimers Dement (Amst). 2016 May 07;3:63-72
pubmed: 27408937
Lancet Neurol. 2013 Jun;12(6):609-22
pubmed: 23684085
Am J Pathol. 2007 Sep;171(3):976-92
pubmed: 17690183
Neurobiol Aging. 1997 May-Jun;18(3):267-73
pubmed: 9263190
PLoS One. 2014 Jun 27;9(6):e100760
pubmed: 24971751
J Biol Chem. 2006 Jul 14;281(28):19296-304
pubmed: 16675464