Dataset Information

Clusterin ameliorates tau pathology in vivo by inhibiting fibril formation.

ABSTRACT: 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.

SUBMITTER: Wojtas AM

PROVIDER: S-EPMC7708249 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Clusterin ameliorates tau pathology in vivo by inhibiting fibril formation.

Wojtas Aleksandra M AM Carlomagno Yari Y Sens Jonathon P JP Kang Silvia S SS Jensen Tanner D TD Kurti Aishe A Baker Kelsey E KE Berry Taylor J TJ Phillips Virginia R VR Castanedes Monica Casey MC Awan Ayesha A DeTure Michael M De Castro Cristhoper H Fernandez CHF Librero Ariston L AL Yue Mei M Daughrity Lillian L Jansen-West Karen R KR Cook Casey N CN Dickson Dennis W DW Petrucelli Leonard L Fryer John D JD

Acta neuropathologica communications 20201201 1

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 assoc ...[more]

PMID: 33261653

Dataset Information

Clusterin ameliorates tau pathology in vivo by inhibiting fibril formation.

Publications

Clusterin ameliorates tau pathology in vivo by inhibiting fibril formation.

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