| First Author | Taylor JM | Year | 2014 |
| Journal | Neurobiol Aging | Volume | 35 |
| Issue | 5 | Pages | 1012-23 |
| PubMed ID | 24262201 | Mgi Jnum | J:212738 |
| Mgi Id | MGI:5582038 | Doi | 10.1016/j.neurobiolaging.2013.10.089 |
| Citation | Taylor JM, et al. (2014) Type-1 interferon signaling mediates neuro-inflammatory events in models of Alzheimer's disease. Neurobiol Aging 35(5):1012-23 |
| abstractText | A neuro-inflammatory response has been implicated in human patients and animal models of Alzheimer's disease (AD). Type-1 interferons are pleiotropic cytokines involved in the initiation and regulation of the pro-inflammatory response; however, their role in AD is unknown. This study investigated the contribution of type-1 IFN signaling in the neuro-inflammatory response to amyloid-beta (Abeta) in vitro and in the APP/PS1 transgenic mouse model of AD. Enzyme-linked immunosorbent assay confirmed a 2-fold increase in IFNalpha in APP/PS1 brains compared with control brains. Quantitative polymerase chain reaction also identified increased IFNalpha and IFNbeta expression in human pre-frontal cortex from AD patients. In vitro studies in primary neurons demonstrated Abeta-induced type-1 IFN expression preceded that of other classical pro-inflammatory cytokines, IL1-beta, and IL-6. Significantly, ablation of type-1 interferon-alpha receptor 1 expression in BE(2)M17 neuroblastoma cells and primary neurons afforded protection against Abeta-induced toxicity. This study supports a role for type-1 interferons in the pro-inflammatory response and neuronal cell death in AD and suggests that blocking type-1 interferon-alpha receptor 1 maybe a therapeutic target to limit the disease progression. |
