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Related Experiment Videos

Complement activation in very early Alzheimer disease.

H Zanjani1, C E Finch, C Kemper

  • 1Andrus Gerontology Center and Department of Biological Science, University of Southern California Los Angeles, California, USA.

Alzheimer Disease and Associated Disorders
|June 9, 2005
PubMed
Summary

The complement system (C) is activated in early Alzheimer

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Area of Science:

  • Neuroscience
  • Immunology
  • Pathology

Background:

  • The complement system plays a role in neuroinflammation.
  • Its involvement in early Alzheimer disease (AD) pathogenesis is not fully understood.

Purpose of the Study:

  • To investigate the activation of the complement system in early-stage Alzheimer disease (AD) and non-demented aging.
  • To determine the stage-specific deposition of complement fragments and regulators in AD brains.

Main Methods:

  • Immunohistochemistry was used to detect complement fragments (C1q, C3, C4, C5b-9) and regulators (CD59, CR1, DAF, MCP) in brain tissue.
  • Subjects were assessed using the Clinical Dementia Rating (CDR) scale.

Main Results:

  • Complement activation (C3, C4) was observed in all brains with amyloid deposits, including non-demented individuals and preclinical AD.

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  • Complement fragment deposition increased with plaque density in AD.
  • Early complement components (C1q, C5b-9) were detected in very mild AD, and consistently in severe AD.
  • Complement regulators were notably absent from plaques and tangles, indicating incomplete control.

    • Conclusions:

    • Complement system activation is an early event in Alzheimer disease pathogenesis, occurring even before clinical symptoms.
    • The deposition of complement fragments correlates with AD progression and amyloid pathology.
    • Incomplete regulation of complement activation in AD suggests a potential therapeutic target.