1. The P522R protective variant of PLCG2 promotes the expression of antigen presentation genes by human microglia in an Alzheimer's disease mouse model
- Author
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Christel Claes, Whitney E. England, Emma P. Danhash, Sepideh Kiani Shabestari, Amit Jairaman, Jean Paul Chadarevian, Jonathan Hasselmann, Andy P. Tsai, Morgan A. Coburn, Jessica Sanchez, Tau En Lim, Jorge L. S. Hidalgo, Christina Tu, Michael D. Cahalan, Bruce T. Lamb, Gary E. Landreth, Robert C. Spitale, Mathew Blurton‐Jones, and Hayk Davtyan
- Subjects
Antigen Presentation ,Amyloid beta-Peptides ,Epidemiology ,Health Policy ,Induced Pluripotent Stem Cells ,Mice, Transgenic ,CD8-Positive T-Lymphocytes ,Mice ,Disease Models, Animal ,Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Alzheimer Disease ,Animals ,Humans ,Microglia ,Neurology (clinical) ,Chemokines ,Geriatrics and Gerontology - Abstract
The P522R variant of PLCG2, expressed by microglia, is associated with reduced risk of Alzheimer's disease (AD). Yet, the impact of this protective mutation on microglial responses to AD pathology remains unknown. Chimeric AD and wild-type mice were generated by transplanting PLCG2-P522R or isogenic wild-type human induced pluripotent stem cell microglia. At 7 months of age, single-cell and bulk RNA sequencing, and histological analyses were performed. The PLCG2-P522R variant induced a significant increase in microglial human leukocyte antigen (HLA) expression and the induction of antigen presentation, chemokine signaling, and T cell proliferation pathways. Examination of immune-intact AD mice further demonstrated that the PLCG2-P522R variant promotes the recruitment of CD8
- Published
- 2022
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