It has become clear that brain immunity encompasses the resident myeloid cells, the microglia, and well as circulating adaptive and innate immune cells, that are located in special compartments at the brain's borders, including the meninges and the choroid plexus. These circulating immune cells support brain repair and functional plasticity. Specifically, we found that the epithelial layer that forms the blood-CSF-barrier, the choroid plexus epithelium (CP), serves as a gate regulating leukocyte entry to the CNS; its activity is controlled by its cytokine milieu, and specifically IFN-γ. In analyzing how the activity of this interface determines the fate of the brain, we discovered by immunogenomics and immunohistochemistry that in aging and in Alzheimer’s disease (AD) mouse models, this interface is suppressed with respect to its ability to allow communication between the brain and the circulating leukocytes.
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