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ResearchIn-Press PreviewNeuroscience
Open Access | 10.1172/JCI152565
1Washington University School of Medicine, St. Louis, United States of America
2Department of Pharmacology and Regenerative Medicine, University of Illinois College of Medicine, Chicago, United States of America
3Department of Neurology, Washington University School of Medicine, St. Louis, United States of America
4Department of Medicine, Washington University School of Medicine, St. Louis, United States of America
5Department of Internal Medicine, Washington University School of Medicine, St. Louis, United States of America
6Department of Surgery, Washington University School of Medicine, St. Louis, United States of America
7Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, United States of America
8Cardiology, University Health Network, Toronto, Canada
Find articles by Yan, P. in: JCI | PubMed | Google Scholar
1Washington University School of Medicine, St. Louis, United States of America
2Department of Pharmacology and Regenerative Medicine, University of Illinois College of Medicine, Chicago, United States of America
3Department of Neurology, Washington University School of Medicine, St. Louis, United States of America
4Department of Medicine, Washington University School of Medicine, St. Louis, United States of America
5Department of Internal Medicine, Washington University School of Medicine, St. Louis, United States of America
6Department of Surgery, Washington University School of Medicine, St. Louis, United States of America
7Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, United States of America
8Cardiology, University Health Network, Toronto, Canada
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1Washington University School of Medicine, St. Louis, United States of America
2Department of Pharmacology and Regenerative Medicine, University of Illinois College of Medicine, Chicago, United States of America
3Department of Neurology, Washington University School of Medicine, St. Louis, United States of America
4Department of Medicine, Washington University School of Medicine, St. Louis, United States of America
5Department of Internal Medicine, Washington University School of Medicine, St. Louis, United States of America
6Department of Surgery, Washington University School of Medicine, St. Louis, United States of America
7Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, United States of America
8Cardiology, University Health Network, Toronto, Canada
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Xiao, Q.
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1Washington University School of Medicine, St. Louis, United States of America
2Department of Pharmacology and Regenerative Medicine, University of Illinois College of Medicine, Chicago, United States of America
3Department of Neurology, Washington University School of Medicine, St. Louis, United States of America
4Department of Medicine, Washington University School of Medicine, St. Louis, United States of America
5Department of Internal Medicine, Washington University School of Medicine, St. Louis, United States of America
6Department of Surgery, Washington University School of Medicine, St. Louis, United States of America
7Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, United States of America
8Cardiology, University Health Network, Toronto, Canada
Find articles by Ma, X. in: JCI | PubMed | Google Scholar
1Washington University School of Medicine, St. Louis, United States of America
2Department of Pharmacology and Regenerative Medicine, University of Illinois College of Medicine, Chicago, United States of America
3Department of Neurology, Washington University School of Medicine, St. Louis, United States of America
4Department of Medicine, Washington University School of Medicine, St. Louis, United States of America
5Department of Internal Medicine, Washington University School of Medicine, St. Louis, United States of America
6Department of Surgery, Washington University School of Medicine, St. Louis, United States of America
7Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, United States of America
8Cardiology, University Health Network, Toronto, Canada
Find articles by Czerniewski, L. in: JCI | PubMed | Google Scholar
1Washington University School of Medicine, St. Louis, United States of America
2Department of Pharmacology and Regenerative Medicine, University of Illinois College of Medicine, Chicago, United States of America
3Department of Neurology, Washington University School of Medicine, St. Louis, United States of America
4Department of Medicine, Washington University School of Medicine, St. Louis, United States of America
5Department of Internal Medicine, Washington University School of Medicine, St. Louis, United States of America
6Department of Surgery, Washington University School of Medicine, St. Louis, United States of America
7Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, United States of America
8Cardiology, University Health Network, Toronto, Canada
Find articles by Liu, H. in: JCI | PubMed | Google Scholar
1Washington University School of Medicine, St. Louis, United States of America
2Department of Pharmacology and Regenerative Medicine, University of Illinois College of Medicine, Chicago, United States of America
3Department of Neurology, Washington University School of Medicine, St. Louis, United States of America
4Department of Medicine, Washington University School of Medicine, St. Louis, United States of America
5Department of Internal Medicine, Washington University School of Medicine, St. Louis, United States of America
6Department of Surgery, Washington University School of Medicine, St. Louis, United States of America
7Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, United States of America
8Cardiology, University Health Network, Toronto, Canada
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1Washington University School of Medicine, St. Louis, United States of America
2Department of Pharmacology and Regenerative Medicine, University of Illinois College of Medicine, Chicago, United States of America
3Department of Neurology, Washington University School of Medicine, St. Louis, United States of America
4Department of Medicine, Washington University School of Medicine, St. Louis, United States of America
5Department of Internal Medicine, Washington University School of Medicine, St. Louis, United States of America
6Department of Surgery, Washington University School of Medicine, St. Louis, United States of America
7Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, United States of America
8Cardiology, University Health Network, Toronto, Canada
Find articles by Yan, Y. in: JCI | PubMed | Google Scholar
1Washington University School of Medicine, St. Louis, United States of America
2Department of Pharmacology and Regenerative Medicine, University of Illinois College of Medicine, Chicago, United States of America
3Department of Neurology, Washington University School of Medicine, St. Louis, United States of America
4Department of Medicine, Washington University School of Medicine, St. Louis, United States of America
5Department of Internal Medicine, Washington University School of Medicine, St. Louis, United States of America
6Department of Surgery, Washington University School of Medicine, St. Louis, United States of America
7Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, United States of America
8Cardiology, University Health Network, Toronto, Canada
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Randolph, G.
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1Washington University School of Medicine, St. Louis, United States of America
2Department of Pharmacology and Regenerative Medicine, University of Illinois College of Medicine, Chicago, United States of America
3Department of Neurology, Washington University School of Medicine, St. Louis, United States of America
4Department of Medicine, Washington University School of Medicine, St. Louis, United States of America
5Department of Internal Medicine, Washington University School of Medicine, St. Louis, United States of America
6Department of Surgery, Washington University School of Medicine, St. Louis, United States of America
7Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, United States of America
8Cardiology, University Health Network, Toronto, Canada
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Epelman, S.
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1Washington University School of Medicine, St. Louis, United States of America
2Department of Pharmacology and Regenerative Medicine, University of Illinois College of Medicine, Chicago, United States of America
3Department of Neurology, Washington University School of Medicine, St. Louis, United States of America
4Department of Medicine, Washington University School of Medicine, St. Louis, United States of America
5Department of Internal Medicine, Washington University School of Medicine, St. Louis, United States of America
6Department of Surgery, Washington University School of Medicine, St. Louis, United States of America
7Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, United States of America
8Cardiology, University Health Network, Toronto, Canada
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Lee, J.
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1Washington University School of Medicine, St. Louis, United States of America
2Department of Pharmacology and Regenerative Medicine, University of Illinois College of Medicine, Chicago, United States of America
3Department of Neurology, Washington University School of Medicine, St. Louis, United States of America
4Department of Medicine, Washington University School of Medicine, St. Louis, United States of America
5Department of Internal Medicine, Washington University School of Medicine, St. Louis, United States of America
6Department of Surgery, Washington University School of Medicine, St. Louis, United States of America
7Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, United States of America
8Cardiology, University Health Network, Toronto, Canada
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Published May 5, 2022 - More info
Microglia, the parenchymal tissue macrophages in the brain, surround amyloid plaques in Alzheimer’s disease (AD) but are ineffective at clearing amyloid to mitigate disease progression. Recent studies in mice indicate that microglia are exclusively derived from primitive yolk-sac hematopoiesis and self-renew without contribution from ontogenically-distinct monocytes/macrophages of definitive ‘adult’ hematopoietic origin. Using genetic fate-mapping to label cells of definitive hematopoietic-origin throughout the life-span, we discovered that circulating monocytes contribute 6% of plaque-associated macrophages in aged AD mice. Moreover, peripheral monocytes contributed to a higher fraction of macrophages in the choroid plexus, meninges and perivascular spaces of aged AD mice versus wild-type controls, indicating enrichment at potential sites for entry into the brain parenchyma. Splenectomy, which markedly reduced circulating Ly6Chi monocytes, also reduced abundance of plaque-associated macrophages of definitive-hematopoietic origin, resulting in increased amyloid plaque load. Together, these results indicate that peripherally-derived monocytes invade the brain parenchyma, targeting amyloid plaques to reduce plaque load.