Different tau species lead to heterogeneous tau pathology propagation and misfolding.

Details

Ressource 1Download: Dujardin et al. 2018.pdf (799.38 [Ko])
State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_B4A31779F7E5
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Different tau species lead to heterogeneous tau pathology propagation and misfolding.
Journal
Acta neuropathologica communications
Author(s)
Dujardin S., Bégard S., Caillierez R., Lachaud C., Carrier S., Lieger S., Gonzalez J.A., Deramecourt V., Déglon N., Maurage C.A., Frosch M.P., Hyman B.T., Colin M., Buée L.
ISSN
2051-5960 (Electronic)
ISSN-L
2051-5960
Publication state
Published
Issued date
29/11/2018
Peer-reviewed
Oui
Volume
6
Number
1
Pages
132
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
Tauopathies are a heterogeneous group of pathologies characterized by tau aggregation inside neurons. Most of them are sporadic but certain tauopathies rely on tau gene (MAPT) mutations. They particularly differ from one to another by their different neuropathological signatures e.g. lesion shapes, regions affected and molecular composition of aggregates. Six isoforms of tau exist, but they do not all co-aggregate in each tauopathy but rather have a unique signature for each one. In some tauopathies such as Alzheimer's disease (AD), tau protein aggregation follows stereotypical anatomical stages. Recent data suggest that this progression is due to an active process of tau protein propagation from neuron-to-neuron. We wondered how tau isoforms or mutations could influence the process of tau aggregation and tau propagation. In human neuropathological material, we found that MAPT mutations induce a faster misfolding compared to tau found in sporadic AD patients. In the rat brain, we observed cell-to-cell transfer of non-pathological tau species irrespective of the tested isoform or presence of a mutation. By contrast, we found that the species of tau impact the propagation of tau pathology markers such as hyperphosphorylation and misfolding. Indeed, misfolding and hyperphosphorylated tau proteins do not spread at the same rate when tau is mutated, or the isoform composition is modified. These results clearly argue for the existence of specific folding properties of tau depending on isoforms or mutations impacting the behavior of pathological tau species.
Keywords
Adult, Aged, Aged, 80 and over, Animals, Brain/metabolism, Brain/pathology, Disease Models, Animal, Disease Progression, Female, Humans, Injections, Intraventricular, Male, Middle Aged, Mutation/genetics, Phosphorylation, Protein Isoforms/genetics, Protein Isoforms/metabolism, Proteostasis Deficiencies/complications, Rats, Rats, Wistar, Severity of Illness Index, Tauopathies/etiology, Tauopathies/genetics, Tauopathies/metabolism, Tauopathies/pathology, tau Proteins/genetics, tau Proteins/metabolism, Alzheimer’s disease, Heterogeneity, Isoforms, Misfolding, Propagation, Tau
Pubmed
Web of science
Open Access
Yes
Create date
13/12/2018 16:31
Last modification date
20/08/2019 15:23
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