Antibody-Mediated Targeting of Tau In Vivo Does Not Require Effector Function and Microglial Engagement
The spread of tau pathology correlates with cognitive decline in Alzheimer’s disease. In vitro, tau antibodies can block cell-to-cell tau spreading. Although mechanisms of anti-tau function in vivo are unknown, effector function might promote microglia-mediated clearance. In this study, we investiga...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2016-08-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124716308683 |
| _version_ | 1819274078888919040 |
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| author | Seung-Hye Lee Claire E. Le Pichon Oskar Adolfsson Valérie Gafner Maria Pihlgren Han Lin Hilda Solanoy Robert Brendza Hai Ngu Oded Foreman Ruby Chan James A. Ernst Danielle DiCara Isidro Hotzel Karpagam Srinivasan David V. Hansen Jasvinder Atwal Yanmei Lu Daniela Bumbaca Andrea Pfeifer Ryan J. Watts Andreas Muhs Kimberly Scearce-Levie Gai Ayalon |
| author_facet | Seung-Hye Lee Claire E. Le Pichon Oskar Adolfsson Valérie Gafner Maria Pihlgren Han Lin Hilda Solanoy Robert Brendza Hai Ngu Oded Foreman Ruby Chan James A. Ernst Danielle DiCara Isidro Hotzel Karpagam Srinivasan David V. Hansen Jasvinder Atwal Yanmei Lu Daniela Bumbaca Andrea Pfeifer Ryan J. Watts Andreas Muhs Kimberly Scearce-Levie Gai Ayalon |
| author_sort | Seung-Hye Lee |
| collection | DOAJ |
| description | The spread of tau pathology correlates with cognitive decline in Alzheimer’s disease. In vitro, tau antibodies can block cell-to-cell tau spreading. Although mechanisms of anti-tau function in vivo are unknown, effector function might promote microglia-mediated clearance. In this study, we investigated whether antibody effector function is required for targeting tau. We compared efficacy in vivo and in vitro of two versions of the same tau antibody, with and without effector function, measuring tau pathology, neuron health, and microglial function. Both antibodies reduced accumulation of tau pathology in Tau-P301L transgenic mice and protected cultured neurons against extracellular tau-induced toxicity. Only the full-effector antibody enhanced tau uptake in cultured microglia, which promoted release of proinflammatory cytokines. In neuron-microglia co-cultures, only effectorless anti-tau protected neurons, suggesting full-effector tau antibodies can induce indirect toxicity via microglia. We conclude that effector function is not required for efficacy, and effectorless tau antibodies may represent a safer approach to targeting tau. |
| first_indexed | 2024-12-23T23:02:43Z |
| format | Article |
| id | doaj.art-b163d59ffd12448093ab9975aa14a02e |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-23T23:02:43Z |
| publishDate | 2016-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-b163d59ffd12448093ab9975aa14a02e2022-12-21T17:26:53ZengElsevierCell Reports2211-12472016-08-011661690170010.1016/j.celrep.2016.06.099Antibody-Mediated Targeting of Tau In Vivo Does Not Require Effector Function and Microglial EngagementSeung-Hye Lee0Claire E. Le Pichon1Oskar Adolfsson2Valérie Gafner3Maria Pihlgren4Han Lin5Hilda Solanoy6Robert Brendza7Hai Ngu8Oded Foreman9Ruby Chan10James A. Ernst11Danielle DiCara12Isidro Hotzel13Karpagam Srinivasan14David V. Hansen15Jasvinder Atwal16Yanmei Lu17Daniela Bumbaca18Andrea Pfeifer19Ryan J. Watts20Andreas Muhs21Kimberly Scearce-Levie22Gai Ayalon23Genentech, South San Francisco, CA 94080, USAGenentech, South San Francisco, CA 94080, USAAC Immune SA, 1015 Lausanne, SwitzerlandAC Immune SA, 1015 Lausanne, SwitzerlandAC Immune SA, 1015 Lausanne, SwitzerlandGenentech, South San Francisco, CA 94080, USAGenentech, South San Francisco, CA 94080, USAGenentech, South San Francisco, CA 94080, USAGenentech, South San Francisco, CA 94080, USAGenentech, South San Francisco, CA 94080, USAGenentech, South San Francisco, CA 94080, USAGenentech, South San Francisco, CA 94080, USAGenentech, South San Francisco, CA 94080, USAGenentech, South San Francisco, CA 94080, USAGenentech, South San Francisco, CA 94080, USAGenentech, South San Francisco, CA 94080, USAGenentech, South San Francisco, CA 94080, USAGenentech, South San Francisco, CA 94080, USAGenentech, South San Francisco, CA 94080, USAAC Immune SA, 1015 Lausanne, SwitzerlandGenentech, South San Francisco, CA 94080, USAAC Immune SA, 1015 Lausanne, SwitzerlandGenentech, South San Francisco, CA 94080, USAGenentech, South San Francisco, CA 94080, USAThe spread of tau pathology correlates with cognitive decline in Alzheimer’s disease. In vitro, tau antibodies can block cell-to-cell tau spreading. Although mechanisms of anti-tau function in vivo are unknown, effector function might promote microglia-mediated clearance. In this study, we investigated whether antibody effector function is required for targeting tau. We compared efficacy in vivo and in vitro of two versions of the same tau antibody, with and without effector function, measuring tau pathology, neuron health, and microglial function. Both antibodies reduced accumulation of tau pathology in Tau-P301L transgenic mice and protected cultured neurons against extracellular tau-induced toxicity. Only the full-effector antibody enhanced tau uptake in cultured microglia, which promoted release of proinflammatory cytokines. In neuron-microglia co-cultures, only effectorless anti-tau protected neurons, suggesting full-effector tau antibodies can induce indirect toxicity via microglia. We conclude that effector function is not required for efficacy, and effectorless tau antibodies may represent a safer approach to targeting tau.http://www.sciencedirect.com/science/article/pii/S2211124716308683 |
| spellingShingle | Seung-Hye Lee Claire E. Le Pichon Oskar Adolfsson Valérie Gafner Maria Pihlgren Han Lin Hilda Solanoy Robert Brendza Hai Ngu Oded Foreman Ruby Chan James A. Ernst Danielle DiCara Isidro Hotzel Karpagam Srinivasan David V. Hansen Jasvinder Atwal Yanmei Lu Daniela Bumbaca Andrea Pfeifer Ryan J. Watts Andreas Muhs Kimberly Scearce-Levie Gai Ayalon Antibody-Mediated Targeting of Tau In Vivo Does Not Require Effector Function and Microglial Engagement Cell Reports |
| title | Antibody-Mediated Targeting of Tau In Vivo Does Not Require Effector Function and Microglial Engagement |
| title_full | Antibody-Mediated Targeting of Tau In Vivo Does Not Require Effector Function and Microglial Engagement |
| title_fullStr | Antibody-Mediated Targeting of Tau In Vivo Does Not Require Effector Function and Microglial Engagement |
| title_full_unstemmed | Antibody-Mediated Targeting of Tau In Vivo Does Not Require Effector Function and Microglial Engagement |
| title_short | Antibody-Mediated Targeting of Tau In Vivo Does Not Require Effector Function and Microglial Engagement |
| title_sort | antibody mediated targeting of tau in vivo does not require effector function and microglial engagement |
| url | http://www.sciencedirect.com/science/article/pii/S2211124716308683 |
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