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Updated: Jul 7, 2025

High-resolution Melting PCR for Complement Receptor 1 Length Polymorphism Genotyping: An Innovative Tool for Alzheimer's Disease Gene Susceptibility Assessment
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Complement-mediated synapse loss in Alzheimer's disease: mechanisms and involvement of risk factors

Lang Wen1, Danlei Bi2, Yong Shen3

  • 1Department of Neurology and Institute on Aging and Brain Disorders, The First Affiliated Hospital of USTC, Neurodegenerative Disease Research Center, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230026, China.

Trends in Neurosciences
|December 21, 2023
PubMed

Insights

The complement system drives synapse loss and cognitive decline in Alzheimer's disease (AD) by over-activating synaptic pruning. Understanding these mechanisms is crucial for developing new AD therapies.

Area of Science:

  • Neuroscience
  • Immunology
  • Pathology

Background:

  • The complement system, a part of innate immunity, plays a critical role in neuronal health.
  • Its dysregulation is increasingly implicated in neurodegenerative diseases like Alzheimer's disease (AD).
  • Synapse loss is a primary correlate of cognitive impairment in AD.

Purpose of the Study:

  • To review recent findings on complement-mediated synapse loss in AD.
  • To summarize the mechanisms driving this process.
  • To discuss the influence of AD risk factors like aging and genetics.

Main Methods:

  • Literature review of recent advances in complement research and AD.
  • Analysis of mechanisms linking complement activation to synaptic pruning.
  • Discussion of the role of aging and genetic risk factors.

Main Results:

  • The complement system is a key mediator of synapse loss in AD.
  • Over-activation of complement-dependent synaptic pruning contributes to excessive synapse elimination.
  • Aging and specific risk genes may exacerbate complement-mediated damage.

Conclusions:

  • Complement-mediated synapse loss is a significant driver of cognitive deficits in AD.
  • Further research is needed to elucidate the precise roles of risk factors.
  • Targeting the complement system presents a potential therapeutic strategy for AD.

Keywords:
cognitive declinegliainnate immunityneurodegenerationneuroinflammationsynaptic pruning

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