A Unique Microglia Type Associated with Restricting Development of Alzheimer’s Disease | Zendy

Hadas KerenShaul | Zendy; Amit Spinrad | Zendy; Assaf Weiner | Zendy; Orit Matcovitch-Natan | Zendy; Raz Dvir-Szternfeld | Zendy; Tyler K. Ulland | Zendy; Eyal David | Zendy; Kuti Baruch | Zendy; David Lara-Astaiso | Zendy; Beáta Tóth | Zendy; Shalev Itzkovitz | Zendy; Marco Colonna | Zendy; Michal Schwartz | Zendy; Ido Amit | Zendy

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A Unique Microglia Type Associated with Restricting Development of Alzheimer’s Disease

Author(s) -

Hadas KerenShaul,

Amit Spinrad,

Assaf Weiner,

Orit Matcovitch-Natan,

Raz Dvir-Szternfeld,

Tyler K. Ulland,

Eyal David,

Kuti Baruch,

David Lara-Astaiso,

Beáta Tóth,

Shalev Itzkovitz,

Marco Colonna,

Michal Schwartz,

Ido Amit

Publication year - 2017

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2017.05.018

Subject(s) - trem2 , microglia , neurodegeneration , biology , cell type , downregulation and upregulation , immune system , alzheimer's disease , neuroscience , genetically modified mouse , disease , intracellular , microbiology and biotechnology , cell , receptor , immunology , transgene , inflammation , pathology , genetics , gene , medicine

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.

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