Type I interferon response drives neuroinflammation and synapse loss in Alzheimer disease

Type I interferon (IFN) is a key cytokine that curbs viral infection and cell malignancy. Previously, we demonstrated a potent IFN immunogenicity of nucleic acid-containing (NA-containing) amyloid fibrils in the periphery. Here, we investigated whether IFN is associated with β-amyloidosis inside the brain and contributes to neuropathology. An IFN-stimulated gene (ISG) signature was detected in the brains of multiple murine Alzheimer disease (AD) models, a phenomenon also observed in WT mouse brain challenged with generic NA-containing amyloid fibrils. In vitro, microglia innately responded to NA-containing amyloid fibrils. In AD models, activated ISG-expressing microglia exclusively surrounded NA+ amyloid β…

• BF
  BrightFocus Foundation

  Awards: A20183775, ADR A20183775
• CA
  Cure Alzheimer's Fund
• NI
  National Institutes of Health

  Awards: AG051812, AG020670, AG057587, AG032051, AG054111