Relevance of host tau in tau seeding and spreading in tauopathies.
aging-related tau astrogliopathy
globular glial tauopathy
primary age-related tauopathy
seeding
spreading
tau
tauopathies
Journal
Brain pathology (Zurich, Switzerland)
ISSN: 1750-3639
Titre abrégé: Brain Pathol
Pays: Switzerland
ID NLM: 9216781
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
18
02
2019
accepted:
26
06
2019
pubmed:
10
8
2019
medline:
14
1
2021
entrez:
10
8
2019
Statut:
ppublish
Résumé
Human tau seeding and spreading occur following intracerebral inoculation of brain homogenates obtained from tauopathies in transgenic mice expressing natural or mutant tau, and in wild-type (WT) mice. The present study was geared to learning about the patterns of tau seeding, the cells involved and the characteristics of tau following intracerebral inoculation of homogenates from primary age-related tauopathy (PART: neuronal 4Rtau and 3Rtau), aging-related tau astrogliopathy (ARTAG: astrocytic 4Rtau) and globular glial tauopathy (GGT: 4Rtau with neuronal deposits and specific tau inclusions in astrocytes and oligodendrocytes). For this purpose, young and adult WT mice were inoculated unilaterally in the hippocampus or in the lateral corpus callosum with sarkosyl-insoluble fractions from PART, ARTAG and GGT cases, and were killed at variable periods of three to seven months. Brains were processed for immunohistochemistry in paraffin sections. Tau seeding occurred in the ipsilateral hippocampus and corpus callosum and spread to the septal nuclei, periventricular hypothalamus and contralateral corpus callosum, respectively. Tau deposits were mainly found in neurons, oligodendrocytes and threads; the deposits were diffuse or granular, composed of phosphorylated tau, tau with abnormal conformation and 3Rtau and 4Rtau independently of the type of tauopathy. Truncated tau at the aspartic acid 421 and ubiquitination were absent. Tau deposits had the characteristics of pre-tangles. A percentage of intracellular tau deposits co-localized with active (phosphorylated) tau kinases p38 and ERK 1/2. Present study shows that seeding and spreading of human tau into the brain of WT mice involves neurons and glial cells, mainly oligodendrocytes, thereby supporting the idea of a primary role of oligodendrogliopathy, together with neuronopathy, in the progression of tauopathies. In addition, it suggests that human tau inoculation modifies murine tau metabolism with the production and deposition of 3Rtau and 4Rtau, and by activation of specific tau kinases in affected cells.
Identifiants
pubmed: 31397930
doi: 10.1111/bpa.12778
pmc: PMC8018022
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
298-318Informations de copyright
© 2019 International Society of Neuropathology.
Références
PLoS One. 2013 Dec 30;8(12):e84849
pubmed: 24386422
Neurobiol Dis. 2015 Jan;73:83-95
pubmed: 25220759
Acta Neuropathol. 2011 Oct;122(4):415-28
pubmed: 21773886
J Neurosci. 2017 Nov 22;37(47):11406-11423
pubmed: 29054878
Acta Neuropathol. 2010 Jul;120(1):21-32
pubmed: 20140439
J Neuropathol Exp Neurol. 2006 Apr;65(4):396-405
pubmed: 16691120
Proc Natl Acad Sci U S A. 1988 Jun;85(11):4051-5
pubmed: 3131773
Acta Neuropathol. 2014 May;127(5):667-83
pubmed: 24531916
Neuron. 2016 Nov 23;92(4):796-812
pubmed: 27974162
J Exp Med. 2016 Nov 14;213(12):2635-2654
pubmed: 27810929
Acta Neuropathol. 2015 Jun;129(6):875-94
pubmed: 25862635
Curr Alzheimer Res. 2005 Jan;2(1):3-18
pubmed: 15977985
Arch Neurol. 2003 May;60(5):698-702
pubmed: 12756133
Acta Neuropathol. 2016 Jan;131(1):87-102
pubmed: 26659578
J Neuropathol Exp Neurol. 2017 Apr 1;76(4):270-288
pubmed: 28340083
Acta Neuropathol. 1991;82(4):239-59
pubmed: 1759558
Neuron. 1989 Apr;2(4):1389-97
pubmed: 2560640
EMBO J. 1995 Apr 3;14(7):1304-13
pubmed: 7729409
J Neurochem. 2000 Feb;74(2):490-500
pubmed: 10646499
Acta Neuropathol. 2015 Feb;129(2):221-37
pubmed: 25534024
Hippocampus. 2007;17(2):98-102
pubmed: 17183532
Cell. 2014 Nov 6;159(4):766-74
pubmed: 25417154
PLoS One. 2012;7(2):e31302
pubmed: 22312444
Proc Natl Acad Sci U S A. 2013 Jun 4;110(23):9535-40
pubmed: 23690619
Nat Cell Biol. 2009 Jul;11(7):909-13
pubmed: 19503072
Mol Psychiatry. 2016 Dec;21(12):1790-1798
pubmed: 26830137
Trends Neurosci. 1998 Oct;21(10):428-33
pubmed: 9786340
J Comp Neurol. 2008 Dec 20;511(6):788-803
pubmed: 18925637
J Neuropathol Exp Neurol. 2015 Oct;74(10):975-99
pubmed: 26360374
J Biochem. 2013 Feb;153(2):139-45
pubmed: 23284000
Nat Rev Neurosci. 2016 Apr;17(4):251-60
pubmed: 26988744
Acta Neuropathol. 2015 Sep;130(3):349-62
pubmed: 26150341
J Cell Biol. 1994 Mar;124(5):769-82
pubmed: 8120098
J Neurochem. 2004 Mar;88(5):1078-90
pubmed: 15009664
Brain Pathol. 2013 Mar;23(2):144-53
pubmed: 22882361
Am J Pathol. 2016 Oct;186(10):2709-22
pubmed: 27497324
Biochim Biophys Acta. 2005 Jan 3;1739(2-3):91-103
pubmed: 15615629
Neuron. 1992 Jan;8(1):159-68
pubmed: 1530909
Brain Pathol. 2018 Nov;28(6):965-985
pubmed: 29396893
Am J Pathol. 1999 Jan;154(1):255-70
pubmed: 9916940
Acta Neuropathol Commun. 2014 Jan 30;2:14
pubmed: 24479894
Science. 1988 Jan 15;239(4837):285-8
pubmed: 3122323
Neuropathol Appl Neurobiol. 2015 Feb;41(1):3-23
pubmed: 25495175
Neuron. 2014 Jun 18;82(6):1271-88
pubmed: 24857020
Brain Pathol. 2017 Sep;27(5):675-690
pubmed: 28805003
Acta Neuropathol. 2015 May;129(5):749-56
pubmed: 25628035
PLoS One. 2019 Jan 22;14(1):e0210864
pubmed: 30668577
Biochemistry. 1994 Aug 16;33(32):9511-22
pubmed: 8068626
Neurotox Res. 2004;6(6):469-75
pubmed: 15658002
Neuropathol Appl Neurobiol. 2015 Feb;41(1):47-58
pubmed: 25399729
Mol Brain. 2017 May 30;10(1):18
pubmed: 28558799
J Neurochem. 1993 Dec;61(6):2071-80
pubmed: 8245963
Brain Res Dev Brain Res. 2003 May 14;142(2):121-7
pubmed: 12711363
Brain Res Mol Brain Res. 1999 May 7;68(1-2):119-28
pubmed: 10320789
J Neuropathol Exp Neurol. 2008 Oct;67(10):963-75
pubmed: 18800011
Acta Neuropathol. 2006 Oct;112(4):389-404
pubmed: 16906426
J Neuropathol Exp Neurol. 2014 Jan;73(1):81-97
pubmed: 24335532
Acta Neuropathol Commun. 2017 Dec 19;5(1):99
pubmed: 29258615
FEBS Lett. 1999 May 14;451(1):39-44
pubmed: 10356980
Neuron. 1989 Oct;3(4):519-26
pubmed: 2484340
PLoS One. 2018 Apr 10;13(4):e0195771
pubmed: 29634760
Acta Neuropathol. 2014 Dec;128(6):755-66
pubmed: 25348064
J Neuropathol Exp Neurol. 2001 Apr;60(4):328-41
pubmed: 11305868
Prog Neurobiol. 2018 Oct;169:24-54
pubmed: 30077775
J Neurosci. 2013 Jan 16;33(3):1024-37
pubmed: 23325240
Brain Pathol. 2017 Sep;27(5):645-674
pubmed: 28804999
Brain Pathol. 2013 May;23(3):342-9
pubmed: 23587140
Acta Neuropathol. 2016 Jan;131(1):27-48
pubmed: 26576562
Acta Neuropathol. 2013 Oct;126(4):537-544
pubmed: 23995422
J Biol Chem. 2016 Jan 15;291(3):1277-88
pubmed: 26565023
Neuron. 2012 Feb 23;73(4):685-97
pubmed: 22365544