The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
Prior activation state shapes the microglia response to antihuman TREM2 in a mouse model of Alzheimer’s disease
Abstract
Significance: Alzheimer’s disease (AD) is the most common dementia; no therapy halts its progression. AD pathology, including amyloid-β (Aβ) plaques, neurofibrillary tangles, and synapse loss, triggers microglial responses that modulate disease course. The TREM2 receptor promotes microglia responses to pathology and a variant, TREM2 R47H , impairs ligand binding and increases AD risk. Employing scRNA-seq, we asked: can an anti-TREM2 antibody, acting as a surrogate ligand, stimulate microglia in mice that accumulate Aβ and express either the common TREM2 variant ( TREM2 CV ) or TREM2 R47H ? One systemic injection of anti-TREM2 restored microglia activation in TREM2 R47H mice but promoted limited activation in mice carrying TREM2 CV , which binds endogenous ligands. Thus, anti-TREM2 can strengthen microglial responses during AD, contingent on preexisting TREM2 engagement and basal activation.
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“Microglia gradually alter their state in the presence of Aβ pathology, a process described as transitional states (t1–t6) from homeostatic to cycling (Cyc-M), IFN-responsive (IFN-R), MHC-II expressing (MHCII) and DAM-like61.”
From Immune checkpoint TIM-3 regulates microglia and Alzheimer’s disease (2025) · cites this paper as [61]
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“A significant difference was found only in human MG8 signature annotated as inflammatory61.”
From Immune checkpoint TIM-3 regulates microglia and Alzheimer’s disease (2025) · cites this paper as [61]
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Cites
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A Unique Microglia Type Associated with Restricting Development of Alzheimer’s Disease
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Variant of TREM2 Associated with the Risk of Alzheimer's Disease
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The Immunological Genome Project: networks of gene expression in immune cells
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Cited by
TREM2 drives microglia response to amyloid-β via SYK-dependent and -independent pathways
Wang, S., Sudan, R., Peng, V., Zhou, Y., Du, S., Yuede, C. M., Lei, T., Hou, J., Cai, Z., Cella, M., et al. (2022) · Cell · doi:10.1016/j.cell.2022.09.033 · Cited by 471
Self-citationHuman microglial state dynamics in Alzheimer’s disease progression
Sun, N., Victor, M. B., Park, Y. P., Xiong, X., Scannail, A. N., Leary, N., Prosper, S., Viswanathan, S., Luna, X., Boix, C. A., et al. (2023) · Cell · doi:10.1016/j.cell.2023.08.037 · Cited by 462
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Self-citationMicroglia in Alzheimer's disease at single-cell level. Are there common patterns in humans and mice?
Chen, Y., & Colonna, M. (2021) · Journal of Experimental Medicine · doi:10.1084/jem.20202717 · Cited by 339
Self-citationMicroglia in Alzheimer’s disease: pathogenesis, mechanisms, and therapeutic potentials
Miao, J., Ma, H., Yang, Y., Liao, Y., Lin, C., Zheng, J., Yu, M., & Lan, J. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1201982 · Cited by 293
Metadata
- Authors
- Ellwanger, D. C., Wang, S., Brioschi, S., Shao, Z., Green, L., Case, R., Yoo, D., Weishuhn, D., Rathanaswami, P., Bradley, J., Rao, S., Cha, D., Luan, P., Sambashivan, S., Gilfillan, S., Hasson, S. A., Foltz, I. N., van Lookeren Campagne, M., & Colonna, M.
- Affiliations
- Genome Analysis Unit, Amgen Research, Amgen Inc., South San Francisco, CA 94080;
- Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110;
- Department of Inflammation and Oncology, Amgen Research, Amgen Inc., South San Francisco, CA 94080;
- Department of Biologics Discovery, Amgen Research, Amgen Inc., Burnaby, BC, V5A1V7 Canada;
- Discovery Attribute Sciences, Amgen Research, Amgen Inc., South San Francisco, CA 94080;
- Department of Biologics Optimization, Amgen Research, Amgen Inc., Thousand Oaks, CA 91320;
- Department of Neuroscience, Amgen Research, Amgen Inc., Cambridge, MA 02142;
- Department of Translational Safety and Bioanalytical Sciences, Amgen Research, Amgen Inc., Thousand Oaks, CA 91320.
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2021-01-14
- Volume
- 118
- Issue
- 3
- ISSN
- 0027-8424
- 1091-6490
- Cited by
- 134
- References
- 44
- Language
- en
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- Ellwanger, D. C., Wang, S., Brioschi, S., Shao, Z., Green, L., Case, R., Yoo, D., Weishuhn, D., Rathanaswami, P., Bradley, J., Rao, S., Cha, D., Luan, P., Sambashivan, S., Gilfillan, S., Hasson, S. A., Foltz, I. N., van Lookeren Campagne, M., & Colonna, M. (2021). Prior activation state shapes the microglia response to antihuman TREM2 in a mouse model of Alzheimer’s disease. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.2017742118
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
