TREM2 deficiency eliminates TREM2+ inflammatory macrophages and ameliorates pathology in Alzheimer’s disease mouse models
| Autor: | Guixiang Xu, Gareth R. Howell, Crystal M. Miller, Richard M. Ransohoff, Taylor R. Jay, James B. Leverenz, Susan M. Staugaitis, J. Colleen Karlo, Oleg Butovsky, Paul J. Cheng, Daniel Margevicius, Gary E. Landreth, Leah C. Graham, Bruce T. Lamb, Gregory L. Sousa, Shane M. Bemiller, Anne C. Cotleur, Sanjay W. Pimplikar, Lynn M. Bekris, Margaret L. Broihier |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Cell type Pathology medicine.medical_specialty Amyloid Immunology Mice Transgenic tau Proteins Inflammation Biology Hippocampus Pathogenesis Alzheimer Disease medicine Animals Humans Immunology and Allergy Receptors Immunologic Aged Amyloid beta-Peptides Membrane Glycoproteins Microglia TREM2 Macrophages Neurodegeneration Brief Definitive Report Age Factors medicine.disease Up-Regulation 3. Good health Disease Models Animal medicine.anatomical_structure Leukocyte Common Antigens Female medicine.symptom Alzheimer's disease |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| Popis: | Jay and colleagues show that TREM2 deficiency reduces the number of macrophages infiltrating the brain and is protective against disease pathogenesis in mouse models of Alzheimer’s disease. 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 CD45hiLy6C+ myeloid cells, but not on P2RY12+ parenchymal microglia. In AD mice deficient for TREM2, the CD45hiLy6C+ 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. |
| Databáze: | OpenAIRE |
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