| First Author | Jendresen C | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 4600 |
| PubMed ID | 30872722 | Mgi Jnum | J:276682 |
| Mgi Id | MGI:6307361 | Doi | 10.1038/s41598-019-40999-4 |
| Citation | Jendresen C, et al. (2019) Systemic LPS-induced Abeta-solubilization and clearance in AbetaPP-transgenic mice is diminished by heparanase overexpression. Sci Rep 9(1):4600 |
| abstractText | Amyloid-beta (Abeta) is the main constituent of amyloid deposits in Alzheimer's disease (AD). The neuropathology is associated with neuroinflammation. Here, we investigated effects of systemic lipopolysaccharide (LPS)-treatment on neuroinflammation and Abeta deposition in AbetaPP-mice and double-transgenic mice with brain expression of AbetaPP and heparanase, an enzyme that degrades HS and generates an attenuated LPS-response. At 13 months of age, the mice received a single intraperitoneal injection of 50 microg LPS or vehicle, and were sacrificed 1.5 months thereafter. Abeta in the brain was analyzed histologically and biochemically after sequential detergent extraction. Neuroinflammation was assessed by CD45 immunostaining and mesoscale cytokine/chemokine ELISA. In single-transgenic mice, LPS-treatment reduced total Abeta deposition and increased Tween-soluble Abeta. This was associated with a reduced CXCL1, IL-1beta, TNF-alpha-level and microgliosis, which correlated with amyloid deposition and total Abeta. In contrast, LPS did not change Abeta accumulation or inflammation marker in the double-transgenic mice. Our findings suggest that a single pro-inflammatory LPS-stimulus, if given sufficient time to act, triggers Abeta-clearance in AbetaPP-transgenic mouse brain. The effects depend on HS and heparanase. |
