| First Author | Marschallinger J | Year | 2020 |
| Journal | Nat Neurosci | Volume | 23 |
| Issue | 2 | Pages | 194-208 |
| PubMed ID | 31959936 | Mgi Jnum | J:287375 |
| Mgi Id | MGI:6406173 | Doi | 10.1038/s41593-019-0566-1 |
| Citation | Marschallinger J, et al. (2020) Lipid-droplet-accumulating microglia represent a dysfunctional and proinflammatory state in the aging brain. Nat Neurosci 23(2):194-208 |
| abstractText | Microglia become progressively activated and seemingly dysfunctional with age, and genetic studies have linked these cells to the pathogenesis of a growing number of neurodegenerative diseases. Here we report a striking buildup of lipid droplets in microglia with aging in mouse and human brains. These cells, which we call 'lipid-droplet-accumulating microglia' (LDAM), are defective in phagocytosis, produce high levels of reactive oxygen species and secrete proinflammatory cytokines. RNA-sequencing analysis of LDAM revealed a transcriptional profile driven by innate inflammation that is distinct from previously reported microglial states. An unbiased CRISPR-Cas9 screen identified genetic modifiers of lipid droplet formation; surprisingly, variants of several of these genes, including progranulin (GRN), are causes of autosomal-dominant forms of human neurodegenerative diseases. We therefore propose that LDAM contribute to age-related and genetic forms of neurodegeneration. |
