Abrogation of type-I interferon signalling alters the microglial response to Aβ1–42
Zachery Moore, Frank Mobilio, Frederick R. Walker, Juliet M. Taylor, Peter J. Crack
Abstract
Abstract Neuroinflammation and accompanying microglial dysfunction are now appreciated to be involved in Alzheimer’s disease (AD) pathogenesis. Critical to the process of neuroinflammation are the type-I interferon (IFN) family of cytokines. Efforts to phenotypically characterize microglia within AD identify distinct populations associated with type-I IFN signalling, yet how this affects underlying microglial function is yet to be fully elucidated. Here we demonstrate that Aβ 1–42 exposure increases bioactive levels of type-I IFN produced by primary microglia alongside increased expression of type-I IFN related genes. Primary microglia isolated from brains of APP swe PS1 ΔE9 mice with ablated type-I IFN signalling show an increased phagocytic ability to uptake FITC-Aβ 1–42 . Correlative assessment of plaque sizes in aged APP swe PS1 ΔE9 mice with abrogated type-I IFN signalling show unchanged deposition levels. Microglia from these mice did however show alterations in morphology. This data further highlights the role of type-I IFN signalling within microglia and identifies a role in phagocytosis. As such, targeting both microglial and global type-I IFN signalling presents as a novel therapeutic strategy for AD management.