Inflammatory Processes — Anti-Inflammatory Therapy

  • Paul S. Aisen
  • Deborah B. Marin
  • Kenneth L. Davis
Part of the Advances in Alzheimer Disease Therapy book series (AADT)

Abstract

Histopathologic studies suggest that inflammatory processes are active at sites of neurodegeneration in Alzheimer’s disease (AD) (see Aisen and Davis, 1994). Acute phase proteins such as a-1 antichymotrypsin (ACT), a-2 macroglobulin and C-reactive protein (CRP) are components of plaques. Interleukins 1 and 6, inflammatory cytokines with the capacity to stimulate expression of acute phase proteins, are present in increased amounts. In addition, early components of the complement cascade are found in the region of neuritic plaques. The cellular component of the inflammatory reaction in the AD brain appears to be the activated microglial cell. These cells bear HLA surface markers, and appear to be closely related to, perhaps derived from, blood-borne mononuclear phagocytes. Activated microglia seem to be involved in the maturation of neuritic plaques.

Keywords

Placebo Arthritis Dementia Diarrhea Methotrexate 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Aisen PS, Marin D, Altstiel L, Goodwin C, Baruch B, Jacobson R, Ryan T and Davis KL (1996): A pilot study of prednisone in Alzheimer’s disease. Dementia (in press).Google Scholar
  2. Aisen PS and Davis KL (1994): Inflammatory mechanisms in Alzheimer’s disease: Implications for therapy. Am J Psychiatry 151:1105–1113.PubMedGoogle Scholar
  3. Breitner JC, Gau BA, Welsh KA, Plassman BL, McDonald WM, Helms MJ and Anthony JC (1994): Inverse association of anti-inflammatory treatments and Alzheimer’s disease: initial results of a co-twin control study. Neurology 44:227–232.PubMedGoogle Scholar
  4. Buxbaum JD, Oishi M, Chen HI, Pinkas-Kramarski R, Jaffe EA, Gandy SE and Greengard P (1992): Cholinergic agonists and interleukin 1 regulate processing and secretion of the Alzheimer b/A4 amyloid protein precursor. Proc Natl Acad Sci USA 89: 10075–10078.PubMedCrossRefGoogle Scholar
  5. Campbell IL, Abraham CR, Masliah E, Kemper P, Inglis JD, Oldstone MBA and Mucke L (1993): Neurologic disease induced in transgenic mice by cerebral overexpression of interleukin 6. Proc Natl Acad Sci USA 90: 10061–10065.PubMedCrossRefGoogle Scholar
  6. Fagarasan MO and Aisen PS (1996): IL-1 and anti-inflammatory drugs modulate Ab cytotoxicity in PC 12 cells. Brain Res (in press).Google Scholar
  7. Giulian D, Li J, Leara B and Keenen C (1994): Phagocytic microglia release cytokines and cytotoxins that regulate the survival of astrocytes and neurons in culture. Neurochem Int 25:227–233.PubMedCrossRefGoogle Scholar
  8. Haass C, Koo EH, Mellon A, Hung AY and Selkoe DJ (1992): Targeting of cell-surface β-amyloid precursor protein to lysosomes: alternative processing into amyloid-bearing fragments. Nature 357:500–503.PubMedCrossRefGoogle Scholar
  9. Magarinos AM, Orchinik M and McEwen BS (1995): Oral administration of corticosterone mimics effects of stress on hippocampal CA3c dendritic structure. Soc for Neurosci Abstr 21:1948.Google Scholar
  10. McEwen BS, Angulo J, Cameron H, Chao HM, Daniels D, Gannon MN, Gould E, Mendelson S, Sakai R, Spencer R and Woolley C (1992): Paradoxical effects of adrenal steroids on the brain: protection versus degeneration. Biol Psychiatry 31:177–199.PubMedCrossRefGoogle Scholar
  11. Rogers J, Kirby LC, Hempelman SR, Berry DL, McGeer PL, Kaszniak AW, Zalinski J, Cofield M, Mansukhani L, Willson P and Kogan F (1993): Clinical trial of indomethacin in Alzheimer’s disease. Neurology 43:1609–1611.PubMedGoogle Scholar
  12. Sapolsky RM, Uno H, Rebert CS et al. (1990): Hippocampal damage associated with prolonged glucocorticoid exposure in primates. J Neurosci 10:1897–1902.Google Scholar
  13. Shirahama T and Cohen AS (1974): Blockage of amyloid induction by colchicine in an animal model. J Exp Med 140:1102–1107.PubMedCrossRefGoogle Scholar
  14. Sperber K, Quraishi H, Kalb TH, Panja A, Stecher V and Mayer L (1993): Selective regulation of cytokine secretion by hydroxychloroquine: Inhibition of interleukin 1 alpha (IL-l-a) and IL-6 in human monocytes and T cells. J Rheumatol 20:803–808.PubMedGoogle Scholar
  15. Wallace SL (1974): Colchicine. Seminars Arthritis Rheum 3:369–381.CrossRefGoogle Scholar
  16. Webster S, O’Barr S and Rogers J (1994): Enhanced aggregation and b structure of amyloid b peptide after coincubation with C1Q. J Neurosci Res 39: 448–456.PubMedCrossRefGoogle Scholar
  17. Zemer D, Livneh A and Langevitz P (1992): Reversal of the nephrotic syndrome by colchicine in amyloidosis of familial Mediterranean fever. Ann Intern Med 116:426.PubMedGoogle Scholar

Copyright information

© Birkhäuser Boston 1997

Authors and Affiliations

  • Paul S. Aisen
    • 1
  • Deborah B. Marin
    • 1
  • Kenneth L. Davis
    • 1
  1. 1.Department of PsychiatryMount Sinai Medical CenterNew YorkUSA

Personalised recommendations