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Heterogeneity of CNS myeloid cells and their roles in neurodegeneration

Abstract

The diseased brain hosts a heterogeneous population of myeloid cells, including parenchymal microglia, perivascular cells, meningeal macrophages and blood-borne monocytes. To date, the different types of brain myeloid cells have been discriminated solely on the basis of their localization, morphology and surface epitope expression. However, recent data suggest that resident microglia may be functionally distinct from bone marrow– or blood-derived phagocytes, which invade the CNS under pathological conditions. During the last few years, research on brain myeloid cells has been markedly changed by the advent of new tools in imaging, genetics and immunology. These methodologies have yielded unexpected results, which challenge the traditional view of brain macrophages. On the basis of these new studies, we differentiate brain myeloid subtypes with regard to their origin, function and fate in the brain and illustrate the divergent features of these cells during neurodegeneration.

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Figure 1: Myeloid cells in the CNS, their origin and their involvement in neurodegeneration.
Figure 2: Loss of CX3CR1 signaling ameliorates amyloid deposition but worsens tau pathology.

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Acknowledgements

The authors wish to thank F.F. Klett for Figure 1, K. Bhaskar and B. Lamb for Figure 2, and K. Kierdorf for fruitful discussion. M.P. was supported by the BMBF-funded Competence Network of Multiple Sclerosis (KKNMS), the Competence Network of Neurodegenerative Disorders (DZNE), the Centre of Chronic Immunodeficiency, the Centre for Biological Signaling Studies, the DFG (SFB 620, FOR1336) and the Hertie-Foundation (Gemeinnützige Hertie-Stiftung). J.P. was supported by the BMBF (Berlin-Brandenburger Center für Regenerative Therapien) and the Deutsche Forschungsgemeinschaft (SFB-TRR43, FOR1336 and the excellence cluster NeuroCure). Research in the S.S.S. laboratory is supported by the National Institutes on Aging, the Adler Foundation and Cure Alzheimer's Fund. The R.M.R. laboratory is supported by the US National Institutes of Health, the National Multiple Sclerosis Society, the Williams Family Fund for Multiple Sclerosis Research and the Nancy Davis Center Without Walls.

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Prinz, M., Priller, J., Sisodia, S. et al. Heterogeneity of CNS myeloid cells and their roles in neurodegeneration. Nat Neurosci 14, 1227–1235 (2011). https://doi.org/10.1038/nn.2923

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