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Neurobiol Aging. 2014 May;35(5):1012-23. doi: 10.1016/j.neurobiolaging.2013.10.089. Epub 2013 Oct 29.

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

Author information

1
Department of Pharmacology, University of Melbourne, Melbourne, Victoria, Australia.
2
Synaptic Neurobiology Laboratory, Mental Health Research Institute, Melbourne, Victoria, Australia.
3
Department of Pharmacology, University of Melbourne, Melbourne, Victoria, Australia. Electronic address: pcrack@unimelb.edu.au.

Abstract

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 (Aβ) in vitro and in the APP/PS1 transgenic mouse model of AD. Enzyme-linked immunosorbent assay confirmed a 2-fold increase in IFNα in APP/PS1 brains compared with control brains. Quantitative polymerase chain reaction also identified increased IFNα and IFNβ expression in human pre-frontal cortex from AD patients. In vitro studies in primary neurons demonstrated Aβ-induced type-1 IFN expression preceded that of other classical pro-inflammatory cytokines, IL1-β, and IL-6. Significantly, ablation of type-1 interferon-α receptor 1 expression in BE(2)M17 neuroblastoma cells and primary neurons afforded protection against Aβ-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-α receptor 1 maybe a therapeutic target to limit the disease progression.

KEYWORDS:

Alzheimer's disease; Interleukin-1β; Interleukin-6; JAK-Stat; Neuro-inflammation; Type-1 interferons

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