Astrocyte-Microglia Cross Talk through Complement Activation Modulates Amyloid Pathology in Mouse Models of Alzheimer's Disease

Increasing evidence supports a role of neuroinflammation in the pathogenesis of Alzheimer's disease (AD). Previously, we identified a neuron-glia signaling pathway whereby Aβ acts as an upstream activator of astroglial nuclear factor kappa B (NF-κB), leading to the release of complement C3, which acts on the neuronal C3a receptor (C3aR) to influence dendritic morphology and cognitive function. Here we report that astrocytic complement activation also regulates Aβ dynamics in vitro and amyloid pathology in AD mouse models through microglial C3aR. We show that in primary microglial cultures, acute C3 or C3a activation promotes, whereas chronic C3/C3a treatment attenuates, microglial phagocytosis and that the…

• NI
  National Institutes of Health

  Awards: AG020670, AG032051, NS076117, U54HD083092, 1S10OD016167
• NI
  National Institute of Child Health and Human Development

  Award: U54HD083092