NFκB-activated astroglial release of complement C3 compromises neuronal morphology and function associated with Alzheimer's disease

Neuron. 2015 Jan 7;85(1):101-115. doi: 10.1016/j.neuron.2014.11.018. Epub 2014 Dec 18.


Abnormal NFκB activation has been implicated in Alzheimer's disease (AD). However, the signaling pathways governing NFκB regulation and function in the brain are poorly understood. We identify complement protein C3 as an astroglial target of NFκB and show that C3 release acts through neuronal C3aR to disrupt dendritic morphology and network function. Exposure to Aβ activates astroglial NFκB and C3 release, consistent with the high levels of C3 expression in brain tissue from AD patients and APP transgenic mice, where C3aR antagonist treatment rescues cognitive impairment. Therefore, dysregulation of neuron-glia interaction through NFκB/C3/C3aR signaling may contribute to synaptic dysfunction in AD, and C3aR antagonists may be therapeutically beneficial.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Protein Precursor / genetics
  • Animals
  • Astrocytes / metabolism*
  • Brain / metabolism
  • Complement C3 / metabolism*
  • Humans
  • Mice
  • Mice, Transgenic
  • Microscopy, Confocal
  • NF-kappa B / metabolism*
  • Neurons / metabolism*
  • Neurons / pathology
  • Receptors, Complement / antagonists & inhibitors
  • Receptors, Complement / metabolism*
  • Signal Transduction


  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Complement C3
  • NF-kappa B
  • Receptors, Complement
  • complement C3a receptor

Associated data

  • GEO/GSE63012