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Alzheimer disease and neuroinflammation

  • Patrick L. McGeer
  • E. G. McGeer
  • K. Yasojima
Conference paper

Abstract

It is now generally accepted that the lesions of Alzheimer disease (AD) are associated with a host of inflammatory molecules, including complement proteins, as well as with many activated microglia. Most inflammatory components are synthesized by brain cells. In order to estimate the intensity of the inflammatory reaction, we have measured the levels of the mRNAs for complement proteins, two complement regulators (CD59 and CI inhibitors), an acute phase reactant (C-reactive protein, CRP) and two microglial markers, (HLA-DR and CDllb), in normal and AD brain. The mRNAs for inflammatory mediators are markedly upregulated in AD tissue while those of the complement inhibitors are almost unchanged. The upregulations for CRP and CDllb in AD hippocampus are comparable to those in osteoarthritic joints. This lends further support to the hypothesis that chronic inflammation may be causing neuronal death in AD.

Keywords

Alzheimer Disease Acute Phase Reactant Complement Protein Complement Regulator Neurobiol Aging 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Akiyama H, McGeer PL (1990) Brain microglia constitutively express β-2 integrins. J Neuroimmunol 30: 81 – 93PubMedCrossRefGoogle Scholar
  2. Jiang H, Robey FA, Gewurz H (1992) Localization of sites through which C-reactive protein binds and activates complement to residues 14–26 and 76–92 of the human Clq A chain. J Exp Med 175: 1373 – 1379PubMedCrossRefGoogle Scholar
  3. McGeer EG, McGeer PL (1998) The future use of complement inhibitors for the treatment of neurological diseases. Drugs 55: 739 – 746PubMedCrossRefGoogle Scholar
  4. McGeer EG, McGeer PL (1999) Brain inflammation in Alzheimer disease and the therapeutic implications. Curr Pharmacol Design 5: 821 – 826Google Scholar
  5. McGeer PL, McGeer EG (1995) The inflammatory response system of brain: implications for therapy of Alzheimer and other neurodegenerative diseases. Brain Res Rev 21: 195 – 218PubMedCrossRefGoogle Scholar
  6. McGeer PL, Itagaki S, Tago H, McGeer EG (1987) Reactive microglia in patients with Fsenile dementia of the Alzheimer type are positive for the histocompatability glycoprotein HLA-DR. Neurosci Lett 79: 195 – 200PubMedCrossRefGoogle Scholar
  7. McGeer PL, Schulzer M, McGeer EG (1996) Arthritis and antiinflammatory agents as negative risk factors for Alzheimer disease: A review of seventeen epidemiological studies. Neurology 47: 425 – 432PubMedGoogle Scholar
  8. Rogers J, Luber-Narod J, Styren SD, Civin WH (1988) Expression of immune system- associated antigen by cells of the human central nervous system. Relationship to the pathology of Alzheimer disease. Neurobiol Aging 9: 339 – 349PubMedCrossRefGoogle Scholar
  9. Rogers J, Kirby LC, Hempelman SR, Berry DL, McGeer PL, Kaszniak AW, Zalinski J, Cofield M, Mansukhani L, Willson P, Kogan F (1993) Clinical trial of indomethacin in Alzheimer’s disease. Neurology 43: 1609 – 1611PubMedGoogle Scholar
  10. Webster S, Lue L-F, Brachova L, Tenner AJ, McGeer PL, Terai K, Walker DG, Bradt B, Cooper NR, Rogers J (1997) Molecular and cellular characterization of the membrane attack complex, C5b-9, in Alzheimer’s disease. Neurobiol Aging 18: 415 – 421Google Scholar
  11. Yasojima K, McGeer EG, McGeer PL (1999a) Complement regulators CI inhibitor and CD59 do not significantly inhibit complement activation in Alzheimer disease. Brain Res 833: 297 – 301CrossRefGoogle Scholar
  12. Yasojima K, Schwab C, McGeer EG, McGeer PL (1999b) Upregulated production and activation of the complement system in Alzheimer disease brain. Am J Pathol 154: 927 – 936CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2000

Authors and Affiliations

  • Patrick L. McGeer
    • 2
  • E. G. McGeer
    • 1
  • K. Yasojima
    • 1
  1. 1.Kinsmen Laboratory of Neurological ResearchDepartment of Psychiatry, University of British ColumbiaVancouverCanada
  2. 2.Kinsmen Laboratory of Neurological ResearchUniversity of British ColumbiaVancouverCanada

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