| First Author | Kiani Shabestari S | Year | 2022 |
| Journal | Cell Rep | Volume | 39 |
| Issue | 11 | Pages | 110961 |
| PubMed ID | 35705056 | Mgi Jnum | J:326053 |
| Mgi Id | MGI:7294009 | Doi | 10.1016/j.celrep.2022.110961 |
| Citation | Kiani Shabestari S, et al. (2022) Absence of microglia promotes diverse pathologies and early lethality in Alzheimer's disease mice. Cell Rep 39(11):110961 |
| abstractText | Microglia are strongly implicated in the development and progression of Alzheimer's disease (AD), yet their impact on pathology and lifespan remains unclear. Here we utilize a CSF1R hypomorphic mouse to generate a model of AD that genetically lacks microglia. The resulting microglial-deficient mice exhibit a profound shift from parenchymal amyloid plaques to cerebral amyloid angiopathy (CAA), which is accompanied by numerous transcriptional changes, greatly increased brain calcification and hemorrhages, and premature lethality. Remarkably, a single injection of wild-type microglia into adult mice repopulates the microglial niche and prevents each of these pathological changes. Taken together, these results indicate the protective functions of microglia in reducing CAA, blood-brain barrier dysfunction, and brain calcification. To further understand the clinical implications of these findings, human AD tissue and iPSC-microglia were examined, providing evidence that microglia phagocytose calcium crystals, and this process is impaired by loss of the AD risk gene, TREM2. |
