Microglial INPP5D limits plaque formation and glial reactivity in the PSAPP mouse model of Alzheimer's disease
| Autor: | Emilie L. Castranio, Philip Hasel, Jean‐Vianney Haure‐Mirande, Angie V. Ramirez Jimenez, B. Wade Hamilton, Rachel D. Kim, Charles G. Glabe, Minghui Wang, Bin Zhang, Sam Gandy, Shane A. Liddelow, Michelle E. Ehrlich |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Alzheimer's & Dementia. |
| ISSN: | 1552-5279 1552-5260 |
| Popis: | The inositol polyphosphate-5-phosphatase D (INPP5D) gene encodes a dual-specificity phosphatase that can dephosphorylate both phospholipids and phosphoproteins. Single nucleotide polymorphisms in INPP5D impact risk for developing late onset sporadic Alzheimer's disease (LOAD).To assess the consequences of inducible Inpp5d knockdown in microglia of APPAt age 6 months, we found that the percent area of 6E10These results demonstrate that conditional Inpp5d downregulation in the PSAPP mouse increases plaque burden and recruitment of microglia to plaques. Spatial transcriptomics highlighted an extended gene expression signature associated with plaques and identified CST7 (cystatin F) as a novel marker of plaques.Inpp5d knockdown increases plaque burden and plaque-associated microglia number. Spatial transcriptomics identifies an expanded plaque-specific gene expression profile. Plaque-induced gene expression is altered by Inpp5d knockdown in microglia. Our plaque-associated gene signature overlaps with human Alzheimer's disease gene networks. |
| Databáze: | OpenAIRE |
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