TREM2 deficiency eliminates TREM2+ inflammatory macrophages and ameliorates pathology in Alzheimer's disease mouse models.
Document Type
Article
Publication Date
3-9-2015
JAX Source
J Exp Med 2015 Mar 9; 212(3):287-95.
Volume
212
Issue
3
First Page
287
Last Page
295
ISSN
1540-9538
PMID
25732305
Abstract
Variants in triggering receptor expressed on myeloid cells 2 (TREM2) confer high risk for Alzheimer's disease (AD) and other neurodegenerative diseases. However, the cell types and mechanisms underlying TREM2's involvement in neurodegeneration remain to be established. Here, we report that TREM2 is up-regulated on myeloid cells surrounding amyloid deposits in AD mouse models and human AD tissue. TREM2 was detected on CD45(hi)Ly6C(+) myeloid cells, but not on P2RY12(+) parenchymal microglia. In AD mice deficient for TREM2, the CD45(hi)Ly6C(+) macrophages are virtually eliminated, resulting in reduced inflammation and ameliorated amyloid and tau pathologies. These data suggest a functionally important role for TREM2(+) macrophages in AD pathogenesis and an unexpected, detrimental role of TREM2 in AD pathology. These findings have direct implications for future development of TREM2-targeted therapeutics.
J Exp Med 2015 Mar 9; 212(3):287-95.
Recommended Citation
Jay T,
Miller C,
Cheng P,
Graham LC,
Bemiller S,
Broihier M,
Xu G,
Margevicius D,
Karlo J,
Sousa G,
Cotleur A,
Butovsky O,
Bekris L,
Staugaitis S,
Leverenz J,
Pimplikar S,
Landreth G,
Howell GR,
Ransohoff R,
Lamb B.
TREM2 deficiency eliminates TREM2+ inflammatory macrophages and ameliorates pathology in Alzheimer's disease mouse models. J Exp Med 2015 Mar 9; 212(3):287-95.