Brain macrophages in neurodegeneration

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.