@article{29b853f530374421b1a4cb0116603dde,
title = "A Unique Microglia Type Associated with Restricting Development of Alzheimer's Disease",
abstract = "Alzheimer's disease (AD) is a detrimental neurodegenerative disease with no effective treatments. Due to cellular heterogeneity, defining the roles of immune cell subsets in AD onset and progression has been challenging. Using transcriptional single-cell sorting, we comprehensively map all immune populations in wild-type and AD-transgenic (Tg-AD) mouse brains. We describe a novel microglia type associated with neurodegenerative diseases (DAM) and identify markers, spatial localization, and pathways associated with these cells. Immunohistochemical staining of mice and human brain slices shows DAM with intracellular/phagocytic Aβ particles. Single-cell analysis of DAM in Tg-AD and triggering receptor expressed on myeloid cells 2 (Trem2)−/− Tg-AD reveals that the DAM program is activated in a two-step process. Activation is initiated in a Trem2-independent manner that involves downregulation of microglia checkpoints, followed by activation of a Trem2-dependent program. This unique microglia-type has the potential to restrict neurodegeneration, which may have important implications for future treatment of AD and other neurodegenerative diseases. Video Abstract",
keywords = "Alzheimer's disease, immunology, microglia, single cell RNA-seq, systems biology",
author = "Hadas Keren-Shaul and Amit Spinrad and Assaf Weiner and Orit Matcovitch-Natan and Raz Dvir-Szternfeld and Ulland, {Tyler K.} and Eyal David and Kuti Baruch and David Lara-Astaiso and Beata Toth and Shalev Itzkovitz and Marco Colonna and Michal Schwartz and Ido Amit",
note = "Funding Information: We thank Genia Brodsky for help with the artwork. We thank M. Esiri and A. Troen for their help in obtaining human brain sections. This work was funded by NIH grants RF1AG05148501 (M.C.) and 5T32CA009547-30 (T.K.U.). M.S. is supported by the Advanced European Research Council (232835), by the EU Seventh Framework Program HEALTH-2011 (279017), Israel Science Foundation (ISF)-Legacy-Bio-Med program (1354/15), the Minerva Foundation, and ISF-Neurology (991/16). M.S. holds the Maurice and Ilse Katz Professorial Chair in Neuroimmunology. I.A. is supported by the HHMI International Scholar award, the European Research Council Consolidator Grant (ERC-COG) 724471-HemTree2.0, the Israel Science Foundation (703/15), the Ernest and Bonnie Beutler Research Program of Excellence in Genomic Medicine, the Helen and Martin Kimmel award for innovative investigation, a Minerva Stiftung research grant, the Israeli Ministry of Science, Technology, and Space, the David and Fela Shapell Family Foundation, the NeuroMac DFG/Transregional Collaborative Research Center Grant, and the Abramson Family Center for Young Scientists. I.A. is the incumbent of the Alan and Laraine Fischer Career Development Chair. A patent application has been filed related to this work. Funding Information: We thank Genia Brodsky for help with the artwork. We thank M. Esiri and A.?Troen for their help in obtaining human brain sections. This work was funded by NIH grants RF1AG05148501 (M.C.) and 5T32CA009547-30 (T.K.U.). M.S. is supported by the Advanced European Research Council (232835), by the EU?Seventh Framework Program HEALTH-2011 (279017), Israel Science Foundation (ISF)-Legacy-Bio-Med program (1354/15), the Minerva Foundation, and ISF-Neurology (991/16). M.S. holds the Maurice and Ilse Katz Professorial Chair in Neuroimmunology. I.A. is supported by the HHMI International Scholar award, the European Research Council Consolidator Grant (ERC-COG) 724471-HemTree2.0, the Israel Science Foundation (703/15), the Ernest and Bonnie Beutler Research Program of Excellence in Genomic Medicine, the Helen and Martin Kimmel award for innovative investigation, a Minerva Stiftung research grant, the Israeli Ministry of Science, Technology, and Space, the David and Fela Shapell Family Foundation, the NeuroMac DFG/Transregional Collaborative Research Center Grant, and the Abramson Family Center for Young Scientists. I.A. is the incumbent of the Alan and Laraine Fischer Career Development Chair. A patent application has been filed related to this work. Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",
year = "2017",
month = jun,
day = "15",
doi = "10.1016/j.cell.2017.05.018",
language = "English",
volume = "169",
pages = "1276--1290.e17",
journal = "Cell",
issn = "0092-8674",
number = "7",
}