The P522R protective variant of PLCG2 promotes the expression of antigen presentation genes by human microglia in an Alzheimer's disease mouse model
| Autor: | 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, Hayk Davtyan |
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| Rok vydání: | 2022 |
| Předmět: |
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 |
| Zdroj: | Alzheimer's & Dementia. 18:1765-1778 |
| ISSN: | 1552-5279 1552-5260 |
| DOI: | 10.1002/alz.12577 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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