Complement and microglia mediate early synapse loss in Alzheimer mouse models

Synapse loss in Alzheimer's disease (AD) correlates with cognitive decline. Involvement of microglia and complement in AD has been attributed to neuroinflammation, prominent late in disease. Here we show in mouse models that complement and microglia mediate synaptic loss early in AD. C1q, the initiating protein of the classical complement cascade, is increased and associated with synapses before overt plaque deposition. Inhibition of C1q, C3, or the microglial complement receptor CR3 reduces the number of phagocytic microglia, as well as the extent of early synapse loss. C1q is necessary for the toxic effects of soluble β-amyloid (Aβ) oligomers on synapses and hippocampal long-term potentiation. Finally,…

• JF
  JPB Foundation
• AR
  Alzheimer's Research Trust
• NI
  National Institutes of Health

  Award: AG000222
• NI
  National Institute of Neurological Disorders and Stroke

  Award: R01NS083845