Fighting Alzheimer’s disease by empowering the innate and adaptive immune system

Munich Psychiatry Lecture Series | MPLS

  • ! Cancelled !
  • Date: Jan 23, 2018
  • Time: 11:00 AM - 12:00 PM (Local Time Germany)
  • Speaker: Michal Schwartz
  • Department of Neurobiology | The Weizmann Institute of Science | Rehovot, Israel
  • Location: Max Planck Institute of Psychiatry
  • Room: Lecture Hall
  • Host: Alon Chen
  • Contact: alon_chen@psych.mpg.de
Fighting Alzheimer’s disease by empowering the innate and adaptive immune system<i></i>
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.

We further found that transiently blocking inhibitory immune checkpoints such as PD-1/PD-L1, regulatory pathways that maintain systemic immune homeostasis and tolerance in several mouse models of AD, was effective in reversing cognitive loss, and in modifying disease pathology. In analyzing the role of the brain myeloid cells, the microglia, under such pathologies, we found by using single cell genomics, that they are also kept under unique checkpoint mechanisms that are desirable in homeostasis, but become counterproductive under disease conditions when robust activity is needed. Overall, our studies suggest that unleashing the immune system rather than treating single neurological disease risk factors, can provide a comprehensive therapy that addresses numerous factors that go awry in the brain. 

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