Type-1 interferon signaling mediates neuro-inflammatory events in models of Alzheimer's disease

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 (A beta) in vitro and in the APP/PS1 transgenic mouse model of AD. Enzyme-linked immunosorbent assay confirmed a 2-fold increase in IFN alpha in APP/PS1 brains compared with control brains. Quantitative polymerase chain reaction also identified increased IFN alpha and IFN beta expression in human pre-frontal cortex from AD patients. In vitro studies in primary neurons demonstrated Ab-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 A beta-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. Crown Copyright (C) 2014 Published by Elsevier Inc. All rights reserved.