Clusterin induced by OPC phagocytosis blocks IL-9 secretion to inhibit myelination in a model of Alzheimer's disease
Background: Variants in the CLUSTERIN gene have been identified as a risk factor for late-onset Alzheimer's disease and are linked to decreased white matter integrity in healthy adults. However, the specific role for clusterin in myelin maintenance in the context of Alzheimer's disease rem...
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| Format: | Article |
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Elsevier
2025-01-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844025000143 |
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| author | Rebecca M. Beiter Tula P. Raghavan Olivia Suchocki Hannah E. Ennerfelt Courtney R. Rivet-Noor Andrea R. Merchak Jennifer L. Phillips Tim Bathe John R. Lukens Stefan Prokop Jeffrey L. Dupree Alban Gaultier |
| author_facet | Rebecca M. Beiter Tula P. Raghavan Olivia Suchocki Hannah E. Ennerfelt Courtney R. Rivet-Noor Andrea R. Merchak Jennifer L. Phillips Tim Bathe John R. Lukens Stefan Prokop Jeffrey L. Dupree Alban Gaultier |
| author_sort | Rebecca M. Beiter |
| collection | DOAJ |
| description | Background: Variants in the CLUSTERIN gene have been identified as a risk factor for late-onset Alzheimer's disease and are linked to decreased white matter integrity in healthy adults. However, the specific role for clusterin in myelin maintenance in the context of Alzheimer's disease remains unclear. Methods: We employed a combination of immunofluorescence and transmission electron microscopy techniques, primary culture of OPCs, and an animal model of Alzheimer's disease. Results: We found that phagocytosis of debris such as amyloid beta, myelin, and apoptotic cells, increases clusterin expression in oligodendrocyte progenitors. We further discovered that exposure to clusterin inhibits differentiation of oligodendrocyte progenitors. Mechanistically, clusterin blunts production of IL-9 and addition of exogenous IL-9 can rescue clusterin-inhibited myelination. Lastly, we demonstrate that clusterin deletion in mice prevents myelin loss in the 5XFAD model. Discussion: Our data suggest that clusterin could play a key role in Alzheimer's disease myelin pathology. |
| format | Article |
| id | doaj-art-a93990a54a01448a92865d9ab748ba8e |
| institution | Kabale University |
| issn | 2405-8440 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj-art-a93990a54a01448a92865d9ab748ba8e2025-01-17T04:51:48ZengElsevierHeliyon2405-84402025-01-01111e41635Clusterin induced by OPC phagocytosis blocks IL-9 secretion to inhibit myelination in a model of Alzheimer's diseaseRebecca M. Beiter0Tula P. Raghavan1Olivia Suchocki2Hannah E. Ennerfelt3Courtney R. Rivet-Noor4Andrea R. Merchak5Jennifer L. Phillips6Tim Bathe7John R. Lukens8Stefan Prokop9Jeffrey L. Dupree10Alban Gaultier11Center for Brain Immunology and Glia, Department of Neuroscience, Charlottesville, VA 22908, USA; Graduate Program in Neuroscience, Charlottesville, VA 22908, USA; Department of Neurobiology, UMass Chan Medical School, Worcester, MA 01655, USA; Corresponding author. Center for Brain Immunology and Glia, Department of Neuroscience, Charlottesville, VA 22908, USA.Center for Brain Immunology and Glia, Department of Neuroscience, Charlottesville, VA 22908, USA; Graduate Program in Neuroscience, Charlottesville, VA 22908, USA; Medical Scientist Training Program, University of Virginia School of Medicine, Charlottesville, VA 22908, USACenter for Brain Immunology and Glia, Department of Neuroscience, Charlottesville, VA 22908, USA; Graduate Program in Neuroscience, Charlottesville, VA 22908, USACenter for Brain Immunology and Glia, Department of Neuroscience, Charlottesville, VA 22908, USA; Graduate Program in Neuroscience, Charlottesville, VA 22908, USACenter for Brain Immunology and Glia, Department of Neuroscience, Charlottesville, VA 22908, USA; Graduate Program in Neuroscience, Charlottesville, VA 22908, USACenter for Brain Immunology and Glia, Department of Neuroscience, Charlottesville, VA 22908, USA; Graduate Program in Neuroscience, Charlottesville, VA 22908, USACenter for Translational Research in Neurodegenerative Disease, College of Medicine, University of Florida, Gainesville, FL, 32610, USA; Department of Pathology, College of Medicine, University of Florida, Gainesville, 32610, USA; McKnight Brain Institute, College of Medicine, University of Florida, Gainesville, FL, 32610, USACenter for Translational Research in Neurodegenerative Disease, College of Medicine, University of Florida, Gainesville, FL, 32610, USA; Department of Pathology, College of Medicine, University of Florida, Gainesville, 32610, USA; McKnight Brain Institute, College of Medicine, University of Florida, Gainesville, FL, 32610, USACenter for Brain Immunology and Glia, Department of Neuroscience, Charlottesville, VA 22908, USA; Graduate Program in Neuroscience, Charlottesville, VA 22908, USACenter for Translational Research in Neurodegenerative Disease, College of Medicine, University of Florida, Gainesville, FL, 32610, USA; Department of Pathology, College of Medicine, University of Florida, Gainesville, 32610, USA; McKnight Brain Institute, College of Medicine, University of Florida, Gainesville, FL, 32610, USADepartment of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA 23298, USACenter for Brain Immunology and Glia, Department of Neuroscience, Charlottesville, VA 22908, USA; Graduate Program in Neuroscience, Charlottesville, VA 22908, USA; Corresponding author. Center for Brain Immunology and Glia, Department of Neuroscience, Charlottesville, VA 22908, USA.Background: Variants in the CLUSTERIN gene have been identified as a risk factor for late-onset Alzheimer's disease and are linked to decreased white matter integrity in healthy adults. However, the specific role for clusterin in myelin maintenance in the context of Alzheimer's disease remains unclear. Methods: We employed a combination of immunofluorescence and transmission electron microscopy techniques, primary culture of OPCs, and an animal model of Alzheimer's disease. Results: We found that phagocytosis of debris such as amyloid beta, myelin, and apoptotic cells, increases clusterin expression in oligodendrocyte progenitors. We further discovered that exposure to clusterin inhibits differentiation of oligodendrocyte progenitors. Mechanistically, clusterin blunts production of IL-9 and addition of exogenous IL-9 can rescue clusterin-inhibited myelination. Lastly, we demonstrate that clusterin deletion in mice prevents myelin loss in the 5XFAD model. Discussion: Our data suggest that clusterin could play a key role in Alzheimer's disease myelin pathology.http://www.sciencedirect.com/science/article/pii/S2405844025000143Oligodendrocyte progenitor cellsAstrocyteClusterinMyelinAlzheimer's diseaseIL-9 |
| spellingShingle | Rebecca M. Beiter Tula P. Raghavan Olivia Suchocki Hannah E. Ennerfelt Courtney R. Rivet-Noor Andrea R. Merchak Jennifer L. Phillips Tim Bathe John R. Lukens Stefan Prokop Jeffrey L. Dupree Alban Gaultier Clusterin induced by OPC phagocytosis blocks IL-9 secretion to inhibit myelination in a model of Alzheimer's disease Heliyon Oligodendrocyte progenitor cells Astrocyte Clusterin Myelin Alzheimer's disease IL-9 |
| title | Clusterin induced by OPC phagocytosis blocks IL-9 secretion to inhibit myelination in a model of Alzheimer's disease |
| title_full | Clusterin induced by OPC phagocytosis blocks IL-9 secretion to inhibit myelination in a model of Alzheimer's disease |
| title_fullStr | Clusterin induced by OPC phagocytosis blocks IL-9 secretion to inhibit myelination in a model of Alzheimer's disease |
| title_full_unstemmed | Clusterin induced by OPC phagocytosis blocks IL-9 secretion to inhibit myelination in a model of Alzheimer's disease |
| title_short | Clusterin induced by OPC phagocytosis blocks IL-9 secretion to inhibit myelination in a model of Alzheimer's disease |
| title_sort | clusterin induced by opc phagocytosis blocks il 9 secretion to inhibit myelination in a model of alzheimer s disease |
| topic | Oligodendrocyte progenitor cells Astrocyte Clusterin Myelin Alzheimer's disease IL-9 |
| url | http://www.sciencedirect.com/science/article/pii/S2405844025000143 |
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