| First Author | Kalovyrna N | Year | 2020 |
| Journal | Sci Rep | Volume | 10 |
| Issue | 1 | Pages | 8670 |
| PubMed ID | 32457323 | Mgi Jnum | J:293272 |
| Mgi Id | MGI:6447894 | Doi | 10.1038/s41598-020-65378-2 |
| Citation | Kalovyrna N, et al. (2020) A 3'UTR modification of the TNF-alpha mouse gene increases peripheral TNF-alpha and modulates the Alzheimer-like phenotype in 5XFAD mice. Sci Rep 10(1):8670 |
| abstractText | Tumor necrosis factor-alpha (TNF-alpha) is a pro-inflammatory cytokine, involved in Alzheimer's disease pathogenesis. Anti-TNF-alpha therapeutic approaches currently used in autoimmune diseases have been proposed as a therapeutic strategy in AD. We have previously examined the role of TNF-alpha and anti-TNF-alpha drugs in AD, using 5XFAD mice, and we have found a significant role for peripheral TNF-alpha in brain inflammation. Here we investigated the role of mouse TNF-alpha on the AD-like phenotype of 5XFAD mice using a knock-in mouse with deletion of the 3'UTR of the endogenous TNF-alpha (TNF(DeltaARE/+)) that develops rheumatoid arthritis and Crohn's disease. 5XFAD/TNF(DeltaARE/+) mice showed significantly decreased amyloid deposition. Interestingly, microglia but not astrocytes were activated in 5XFAD/ TNF(DeltaARE/+) brains. This microglial activation was associated with increased infiltrating peripheral leukocytes and perivascular macrophages and synaptic degeneration. APP levels and APP processing enzymes involved in Abeta production remained unchanged, suggesting that the reduced amyloid burden can be attributed to the increased microglial and perivascular macrophage activation caused by TNF-alpha. Peripheral TNF-alpha levels were increased while brain TNF-alpha remained the same. These data provide further evidence for peripheral TNF-alpha as a mediator of inflammation between the periphery and the brain. |
