Science· 2016Q1
Complement and microglia mediate early synapse loss in Alzheimer mouse models
- 3,392citations
- Q1SCImago
- 2016year
Short summary
In Alzheimer's disease models, complement protein C1q and microglia drive early synapse loss before plaque formation, a process previously thought to occur later and be driven by neuroinflammation.
AI-generated from the title and abstract; the full text is not read.
Key points
- C1q protein is found at synapses before overt plaque deposition in AD mouse models.
- Inhibiting C1q, C3, or microglial CR3 receptor reduced early synapse loss.
- Microglia engulf synaptic material in a CR3-dependent manner when exposed to soluble Aβ oligomers.
- C1q is essential for the detrimental effects of soluble Aβ oligomers on synapses and long-term potentiation.
AI-generated from the title and abstract; the full text is not read.
Abstract
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, microglia in adult brains engulf synaptic material in a CR3-dependent process when exposed to soluble Aβ oligomers. Together, these findings suggest that the complement-dependent pathway and microglia that prune excess synapses in development are inappropriately activated and mediate synapse loss in AD.
The authors' abstract, as published at the source. Science, 2016 · DOI ↗
Continue with a free account
Ask the paper: 3 free questions a day about this paper; save it, get its citation, new summaries every day for your field. Takeaways are Premium.
Continue free on the webSign in with Google or Apple; no card needed. You come back to this paper.
On your phone:
Field: Neurology (Neuroscience)
NeurologyNeuroscience