| First Author | Pons V | Year | 2021 |
| Journal | Alzheimers Res Ther | Volume | 13 |
| Issue | 1 | Pages | 8 |
| PubMed ID | 33402196 | Mgi Jnum | J:329601 |
| Mgi Id | MGI:6823312 | Doi | 10.1186/s13195-020-00747-7 |
| Citation | Pons V, et al. (2021) Conditional genetic deletion of CSF1 receptor in microglia ameliorates the physiopathology of Alzheimer's disease. Alzheimers Res Ther 13(1):8 |
| abstractText | BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common form of dementia in the world. Microglia are the innate immune cells of CNS; their proliferation, activation, and survival in pathologic and healthy brain have previously been shown to be highly dependent on CSF1R. METHODS: Here, we investigate the impact of such receptor on AD etiology and microglia. We deleted CSF1R using Cre/Lox system; the knockout (KO) is restricted to microglia in the APP/PS1 mouse model. We induced the knockout at 3 months old, before plaque formation, and evaluated both 6- and 8-month-old groups of mice. RESULTS: Our findings demonstrated that CSF1R KO did not impair microglial survival and proliferation at 6 and 8 months of age in APP cKO compared to their littermate-control groups APPSwe/PS1. We have also shown that cognitive decline is delayed in CSF1R-deleted mice. Ameliorations of AD etiology are associated with a decrease in plaque volume in the cortex and hippocampus area. A compensating system seems to take place following the knockout, since TREM2/beta-Catenin and IL-34 expression are significantly increased. Such a compensatory mechanism may promote microglial survival and phagocytosis of Abeta in the brain. CONCLUSIONS: Our results provide new insights on the role of CSF1R in microglia and how it interacts with the TREM2/beta-Catenin and IL-34 system to clear Abeta and ameliorates the physiopathology of AD. |
