The choroid plexus in inflammatory and degenerative diseases of the central nervous system

Supporting the health and function of the central nervous system (CNS), the choroid plexus (CP) not only produces cerebrospinal fluid, but it also facilitates brain-immune interfacing, removes waste, and secretes proneuronal signals. Despite these key physiological contributions, a pathogenic role for the CP in promoting neurologic disease has been relatively underappreciated. Resident CNS cells, including microglia, and peripheral immune cells, such as lymphocytes and macrophages, can interact to promote inflammatory changes within the brain. Such an environment, rich in cytokines and antibodies, can be neurotoxic and produce the symptoms of neuroinflammatory diseases. In other conditions, poorly understood metabolic and cellular disturbances damage neurons and their support cells, such as oligodendrocytes. The progressive loss of functionally intact neuronal networks is responsible for the sequelae of neurodegenerative diseases. Originally described as separate entities, neuroinflammatory and neurodegenerative conditions nevertheless actually share several remarkable similarities. Research indicates that these diverse neurologic pathologies are linked by core CP aberrations, including infiltration by peripheral immune cells, enhanced leukocyte transmigration, paracellular barrier breakdown, synthesis of inflammatory signals, impaired clearance of cerebrospinal fluid neurotoxins, and diminished neurotrophic factor release. This review article highlights recent advances in understanding CP deficits in several prominent inflammatory and degenerative conditions of the CNS. Importantly, the evident intersection between these two categories emphasizes the need to study them in parallel. In doing so, much-needed advances can be made in understanding and managing both neuroinflammation and neurodegeneration.