Clusterin ameliorates tau pathology in vivo by inhibiting fibril formation.
Alzheimer’s disease
Clusterin
Tau
Tauopathy
Journal
Acta neuropathologica communications
ISSN: 2051-5960
Titre abrégé: Acta Neuropathol Commun
Pays: England
ID NLM: 101610673
Informations de publication
Date de publication:
01 12 2020
01 12 2020
Historique:
received:
09
11
2020
accepted:
11
11
2020
entrez:
2
12
2020
pubmed:
3
12
2020
medline:
10
11
2021
Statut:
epublish
Résumé
The molecular chaperone Clusterin (CLU) impacts the amyloid pathway in Alzheimer's disease (AD) but its role in tau pathology is unknown. We observed CLU co-localization with tau aggregates in AD and primary tauopathies and CLU levels were upregulated in response to tau accumulation. To further elucidate the effect of CLU on tau pathology, we utilized a gene delivery approach in CLU knock-out (CLU KO) mice to drive expression of tau bearing the P301L mutation. We found that loss of CLU was associated with exacerbated tau pathology and anxiety-like behaviors in our mouse model of tauopathy. Additionally, we found that CLU dramatically inhibited tau fibrilization using an in vitro assay. Together, these results demonstrate that CLU plays a major role in both amyloid and tau pathologies in AD.
Identifiants
pubmed: 33261653
doi: 10.1186/s40478-020-01079-1
pii: 10.1186/s40478-020-01079-1
pmc: PMC7708249
doi:
Substances chimiques
CLU protein, human
0
Clu protein, mouse
0
Clusterin
0
Mapt protein, mouse
0
tau Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
210Subventions
Organisme : NINDS NIH HHS
ID : R35 NS097273
Pays : United States
Organisme : NIH HHS
ID : AG057997
Pays : United States
Organisme : NIH HHS
ID : AG062110
Pays : United States
Organisme : NINDS NIH HHS
ID : P01 NS084974
Pays : United States
Organisme : National Institutes of Health (US)
ID : NS084974
Organisme : NIH HHS
ID : NS094137
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG063780
Pays : United States
Organisme : NIH HHS
ID : AG062077
Pays : United States
Organisme : NIH HHS
ID : AG062556
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG062077
Pays : United States
Organisme : NIH HHS
ID : NS110435
Pays : United States
Organisme : NIH HHS
ID : AG047327
Pays : United States
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