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Brain macrophages in neurodegeneration
Rachel J Johnston1, Nicole A Pagán Torres1, Yangchen Li1
1Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO, United States; Brain Immunology and Glia (BIG) Center, Washington University in St. Louis School of Medicine, St. Louis, MO, United States.
Abstract:
Brain macrophages are not uniform responders to neurodegeneration, but anatomically specialized populations whose functions depend on niche, developmental history, and regulatory state. The goal of this chapter is to discuss how parenchymal microglia and brain border associated macrophages as components of a distributed macrophage network that operates across the central nervous system. Microglia are embedded within the parenchyma and are central to surveillance, synaptic remodeling, myelin maintenance and tissue repair, whereas BAMs occupy vascular, meningeal, and choroid plexus interfaces where they regulate barrier function, immune surveillance, fluid dynamics and solute clearance. Across disease settings, these populations repeatedly converge and diverge on pathological programs, including inflammatory activation, lysosomal stress, lipid handling and maladaptive crosstalk with neighboring cells. Future studies on how these populations are alike and different and development of technology to allow precise targeting of these populations will be essential towards enhancing macrophage protection of the brain.
Insights
Brain macrophages, including microglia and border-associated macrophages (BAMs), are specialized cells. Understanding their distinct roles in neurodegeneration is key to developing new brain protection strategies.
Area of Science:
- Neuroimmunology
- Cellular Biology
- Neuroscience
Background:
- Brain macrophages are diverse, with functions influenced by their location, development, and state.
- Parenchymal microglia and brain border-associated macrophages (BAMs) form a network within the central nervous system.
- These macrophages have distinct roles in brain health and disease.
Purpose of the Study:
- To discuss the specialized roles of parenchymal microglia and BAMs.
- To explore their functions as components of a distributed macrophage network.
- To highlight their involvement in neurodegenerative disease pathways.
Main Methods:
- This chapter synthesizes current knowledge on brain macrophage populations.
- It reviews their anatomical specialization and functional divergence.
- It discusses their roles in various disease contexts.
Main Results:
- Microglia are crucial for brain surveillance, synaptic plasticity, myelin maintenance, and repair.
- BAMs manage barrier functions, immune surveillance, fluid dynamics, and solute clearance at CNS interfaces.
- Both populations exhibit convergent and divergent pathological responses in disease, including inflammation and lipid handling.
Conclusions:
- Brain macrophages are not uniform; microglia and BAMs have specialized functions.
- Understanding their similarities and differences is vital for brain protection.
- Developing technologies for precise targeting of these macrophage populations is essential for future therapeutic strategies.
