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 fur...
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| Format: | Article |
| Language: | English |
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BMC
2020-12-01
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| Series: | Acta Neuropathologica Communications |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40478-020-01079-1 |
| _version_ | 1818645953657176064 |
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| author | Aleksandra M. Wojtas Yari Carlomagno Jonathon P. Sens Silvia S. Kang Tanner D. Jensen Aishe Kurti Kelsey E. Baker Taylor J. Berry Virginia R. Phillips Monica Casey Castanedes Ayesha Awan Michael DeTure Cristhoper H. Fernandez De Castro Ariston L. Librero Mei Yue Lillian Daughrity Karen R. Jansen-West Casey N. Cook Dennis W. Dickson Leonard Petrucelli John D. Fryer |
| author_facet | Aleksandra M. Wojtas Yari Carlomagno Jonathon P. Sens Silvia S. Kang Tanner D. Jensen Aishe Kurti Kelsey E. Baker Taylor J. Berry Virginia R. Phillips Monica Casey Castanedes Ayesha Awan Michael DeTure Cristhoper H. Fernandez De Castro Ariston L. Librero Mei Yue Lillian Daughrity Karen R. Jansen-West Casey N. Cook Dennis W. Dickson Leonard Petrucelli John D. Fryer |
| author_sort | Aleksandra M. Wojtas |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-17T00:38:56Z |
| format | Article |
| id | doaj.art-fe6771b48e634b8d8a968a11735cfc6c |
| institution | Directory Open Access Journal |
| issn | 2051-5960 |
| language | English |
| last_indexed | 2024-12-17T00:38:56Z |
| publishDate | 2020-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj.art-fe6771b48e634b8d8a968a11735cfc6c2022-12-21T22:10:04ZengBMCActa Neuropathologica Communications2051-59602020-12-018111110.1186/s40478-020-01079-1Clusterin ameliorates tau pathology in vivo by inhibiting fibril formationAleksandra M. Wojtas0Yari Carlomagno1Jonathon P. Sens2Silvia S. Kang3Tanner D. Jensen4Aishe Kurti5Kelsey E. Baker6Taylor J. Berry7Virginia R. Phillips8Monica Casey Castanedes9Ayesha Awan10Michael DeTure11Cristhoper H. Fernandez De Castro12Ariston L. Librero13Mei Yue14Lillian Daughrity15Karen R. Jansen-West16Casey N. Cook17Dennis W. Dickson18Leonard Petrucelli19John D. Fryer20Department of Neuroscience, Mayo ClinicDepartment of Neuroscience, Mayo ClinicDepartment of Neuroscience, Mayo ClinicDepartment of Neuroscience, Mayo ClinicDepartment of Neuroscience, Mayo ClinicDepartment of Neuroscience, Mayo ClinicDepartment of Neuroscience, Mayo ClinicDepartment of Neuroscience, Mayo ClinicDepartment of Neuroscience, Mayo ClinicDepartment of Neuroscience, Mayo ClinicDepartment of Neuroscience, Mayo ClinicDepartment of Neuroscience, Mayo ClinicDepartment of Neuroscience, Mayo ClinicDepartment of Neuroscience, Mayo ClinicDepartment of Neuroscience, Mayo ClinicDepartment of Neuroscience, Mayo ClinicDepartment of Neuroscience, Mayo ClinicDepartment of Neuroscience, Mayo ClinicDepartment of Neuroscience, Mayo ClinicDepartment of Neuroscience, Mayo ClinicDepartment of Neuroscience, Mayo ClinicAbstract 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.https://doi.org/10.1186/s40478-020-01079-1ClusterinAlzheimer’s diseaseTauopathyTau |
| spellingShingle | Aleksandra M. Wojtas Yari Carlomagno Jonathon P. Sens Silvia S. Kang Tanner D. Jensen Aishe Kurti Kelsey E. Baker Taylor J. Berry Virginia R. Phillips Monica Casey Castanedes Ayesha Awan Michael DeTure Cristhoper H. Fernandez De Castro Ariston L. Librero Mei Yue Lillian Daughrity Karen R. Jansen-West Casey N. Cook Dennis W. Dickson Leonard Petrucelli John D. Fryer Clusterin ameliorates tau pathology in vivo by inhibiting fibril formation Acta Neuropathologica Communications Clusterin Alzheimer’s disease Tauopathy Tau |
| title | Clusterin ameliorates tau pathology in vivo by inhibiting fibril formation |
| title_full | Clusterin ameliorates tau pathology in vivo by inhibiting fibril formation |
| title_fullStr | Clusterin ameliorates tau pathology in vivo by inhibiting fibril formation |
| title_full_unstemmed | Clusterin ameliorates tau pathology in vivo by inhibiting fibril formation |
| title_short | Clusterin ameliorates tau pathology in vivo by inhibiting fibril formation |
| title_sort | clusterin ameliorates tau pathology in vivo by inhibiting fibril formation |
| topic | Clusterin Alzheimer’s disease Tauopathy Tau |
| url | https://doi.org/10.1186/s40478-020-01079-1 |
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