TY - JOUR
T1 - A Unique Microglia Type Associated with Restricting Development of Alzheimer's Disease
AU - Keren-Shaul, Hadas
AU - Spinrad, Amit
AU - Weiner, Assaf
AU - Matcovitch-Natan, Orit
AU - Dvir-Szternfeld, Raz
AU - Ulland, Tyler K.
AU - David, Eyal
AU - Baruch, Kuti
AU - Lara-Astaiso, David
AU - Toth, Beata
AU - Itzkovitz, Shalev
AU - Colonna, Marco
AU - Schwartz, Michal
AU - Amit, Ido
PY - 2017/6/15
Y1 - 2017/6/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85020287843&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2017.05.018
DO - 10.1016/j.cell.2017.05.018
M3 - Article
SN - 0092-8674
VL - 169
SP - 1276-1290.e17
JO - Cell
JF - Cell
IS - 7
ER -