| First Author | Czirr E | Year | 2017 |
| Journal | J Exp Med | Volume | 214 |
| Issue | 4 | Pages | 1081-1092 |
| PubMed ID | 28298456 | Mgi Jnum | J:241870 |
| Mgi Id | MGI:5903802 | Doi | 10.1084/jem.20162011 |
| Citation | Czirr E, et al. (2017) Microglial complement receptor 3 regulates brain Abeta levels through secreted proteolytic activity. J Exp Med 214(4):1081-1092 |
| abstractText | Recent genetic evidence supports a link between microglia and the complement system in Alzheimer's disease (AD). In this study, we uncovered a novel role for the microglial complement receptor 3 (CR3) in the regulation of soluble beta-amyloid (Abeta) clearance independent of phagocytosis. Unexpectedly, ablation of CR3 in human amyloid precursor protein-transgenic mice results in decreased, rather than increased, Abeta accumulation. In line with these findings, cultured microglia lacking CR3 are more efficient than wild-type cells at degrading extracellular Abeta by secreting enzymatic factors, including tissue plasminogen activator. Furthermore, a small molecule modulator of CR3 reduces soluble Abeta levels and Abeta half-life in brain interstitial fluid (ISF), as measured by in vivo microdialysis. These results suggest that CR3 limits Abeta clearance from the ISF, illustrating a novel role for CR3 and microglia in brain Abeta metabolism and defining a potential new therapeutic target in AD. |
