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Fig. 9 | Acta Neuropathologica Communications

Fig. 9

From: Deletion of the type-1 interferon receptor in APPSWE/PS1ΔE9 mice preserves cognitive function and alters glial phenotype

Fig. 9

Schematic of the modulated neuro-inflammatory environment in APPSWE/PS1ΔE9 x IFNAR1−/− mice. The current study provides evidence that a type-1 IFN response contributes to the neuro-inflammation observed in AD. Amyloid plaques and soluble Aβ1-42 within the plaque microenvironment triggers pro-inflammatory microglial activation and secretion of pro-inflammatory cytokines, initiating the neuro-inflammatory process. The pro-inflammatory cues within the plaque microenvironment further enhance gliosis, exacerbating inflammation. In AD, excessive Aβ production maintains the stimulus for a pro-inflammatory response, compromising resolution, and contributes to a self-perpetuating neuro-degenerative inflammatory cycle. The current study demonstrates that type-1 IFN signaling intricately controls this neuro-inflammation. Removal of IFNAR1 in APPSWE/PS1ΔE9 mice reduced type-1 IFN production, TNFα expression and conferred an anti-inflammatory and neuro-protective anti-inflammatory activation state of microglia. Enhanced astrocyte reactivity and IL-1β expression, but decreased total microgliosis, was also demonstrated in these mice which were protected from spatial learning and memory deficits at 9 months of age

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