The P522R protective variant of PLCG2 promotes the expression of antigen presentation genes by human microglia in an Alzheimer's disease mouse model

Feb 10, 2022Alzheimer's & dementia : the journal of the Alzheimer's Association

Protective PLCG2 gene variant increases immune activation in brain support cells in an Alzheimer's mouse model

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Abstract

The -P522R variant is associated with increased microglial human leukocyte antigen expression and T cell recruitment in Alzheimer's disease models.

  • The PLCG2-P522R variant may enhance microglial responses to Alzheimer's disease pathology.
  • Increased expression of human leukocyte antigen () was observed in microglia carrying the PLCG2-P522R variant.
  • The variant is linked to the activation of pathways related to antigen presentation, chemokine signaling, and T cell proliferation.
  • Recruitment of CD8T cells to the brain was promoted in immune-intact Alzheimer's disease mice with the PLCG2-P522R variant.
  • These findings suggest a transcriptional state in microglia that may be diminished in Alzheimer's disease patients.

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Key numbers

significant increase
Increase in CD8T Cells
CD8T cell count in -P522R KI 5XFAD mice vs. WT 5XFAD mice
significant increase
-DR Expression
-DR levels in P522R xMGs compared to WT xMGs

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