TREM2 deficiency eliminates TREM2+ inflammatory macrophages and ameliorates pathology in Alzheimer’s disease mouse models

By T. Jay, Crystal M Miller, Paul J. Cheng, Leah C. Graham, S. Bemiller, Margaret L Broihier, Guixiang Xu, Daniel Margevicius, J. Karlo, Gregory L. Sousa and 10 more. Journal of Experimental Medicine, 2015

629 citations recorded by the source corpus.

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.

Subfields: Immunology, Neurology

View Paper: https://www.semanticscholar.org/paper/5f0fd1cb48f9f7b8e95e0216716a668f2b29c0fa

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. D. Holtzman
2. M. Colonna
3. O. Butovsky
4. Morgan Sheng
5. Hans Lassmann
6. Zhiping Weng
7. B. West
8. Howard L. Weiner

In Neurology

1. D. Holtzman
2. Hans Lassmann
3. M. Colonna
4. Christian Haass
5. Howard L. Weiner
6. O. Butovsky
7. J. Long

Citations in the corpus

• The TREM2-APOE pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases (2017, background): “Consistent with previous findings (Jay et al., 2015), the Ab-plaque load was decreased in APP-PS1:Trem2 / mice (Figure 5H).”
• Amyloid β-based therapy for Alzheimer’s disease: challenges, successes and future (2023, background): “Aβ plaques in AD model mice.(174,175,178) The reduction of TREM2 in Aβ-associated macrophages also altered astrocytosis detected by glial fibrillary acidic protein (GFAP) and S100β.”
• A Unique Microglia Type Associated with Restricting Development of Alzheimer's Disease. (2017, neutral): “, 2013) and Trem2 deficiency in an AD mouse model accelerated Ab plaque accumulation and neuronal loss (Jay et al., 2015; Wang et al., 2015, 2016; Yuan et al., 2016).”
• TREM2-mediated early microglial response limits diffusion and toxicity of amyloid plaques (2016, background): “In 4-mo-old APP PS1-21 mice lacking TREM2, however, hippocampal Aβ accumulation was paradoxically reduced despite the myeloid cell defect, a finding that was interpreted to indicate that TREM2 deficiency protects against AD pathogenesis (Jay et al., 2015).”
• Eliminating microglia in Alzheimer's mice prevents neuronal loss without modulating amyloid-β pathology. (2016, methodology): “One study suggested that the reduction in these cells was due to a lack of infiltrating monocytes from the periphery (Jay et al., 2015)—as monocytes are not eliminated with the doses of CSF1R inhibitors used in this study (Chitu et al.”
• Microglia in Alzheimer’s disease (2018, background): “TREM2-deficient microglia fail to congregate or proliferate around plaques, lack the typical morphological changes of microglial activation, and show increased apoptosis (Jay et al., 2015; Wang et al., 2015, 2016; Mazaheri et al., 2017).”
• Role of neuroinflammation in neurodegeneration development (2023, methodology): “Using the same model, TREM2 deficiency was also found to eliminate macrophages, attenuating inflammation and amyloid/tau pathologies.(229) In distinct tau mouse models, TREM2 deletion have yielded more diverse results.”