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Degradation of Tryptophan in Neurodegenerative Disorders

  • B. Widner
  • F. Leblhuber
  • J. Walli
  • G. P. Tilz
  • U. Demel
  • D. Fuchs
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 467)

Abstract

In patients with neurodegenerative disorders, namely Alzheimer’s disease and Huntington’s disease, we compared serum concentrations of tryptophan, kynurenine and the kynurenine per tryptophan ratio with concentrations of soluble immune activation markers. Significantly lower tryptophan concentrations were observed in the patients, and lower tryptophan levels as well as higher kynurenine levels and higher kynurenine per tryptophan ratios correlated with higher concentrations of neopterin, and soluble receptors for TNF and interleukin-2. In both groups of patients tryptophan concentrations correlated inversely with the degree of mental retardation. No such association existed for the duration of the disease. The data show that systemic chronic immune activation in patients with Alzheimer’s disease and Huntingtons disease is associated with significant degradation of tryptophan, which is most likely due to activation of indoleamine (2,3)-dioxygenase by immunologic stimuli. Further studies will be necessary to investigate a potential role of tryptophan degradation in the pathogenesis of neurodegenerative disorders.

Keywords

Neurodegenerative Disorder Immune Activation Quinolinic Acid Kynurenine Pathway Tryptophan Metabolism 
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. Aisen, P.S. and Davis, K.L., 1994, Inflammatory mechanisms in Alzheimer’s disease: implications for therapy, Am. J. Psych. 151:1105–1113.Google Scholar
  2. Beal, M.F., 1995, Aging, energy, and oxidative stress in neurodegenerative diseases, Ann. Neurol. 38:357–366.PubMedCrossRefGoogle Scholar
  3. Blass, J.B., 1993, Pathophysiology of the Alzheimer’s syndrome, Neurology 43(Suppl 4), 25–38.Google Scholar
  4. Diez-Ruiz, A, Tilz, G.P., Zangerle, R., Baier-Bitterlich, G., Wachter, H., and Fuchs, D., 1995, Soluble receptors for tumor necrosis factor in clinical laboratory diagnosis, Eur. J. Haematol. 54:1–8.PubMedCrossRefGoogle Scholar
  5. Freese, A., Swartz, K.J., During, M.J., and Martin, J.B., 1990, Kynurenine metabolites of tryptophan: Implications for neurological diseases, Neurology 40:691–695.PubMedCrossRefGoogle Scholar
  6. Fuchs, D., Malkowsky, M, Reibnegger, G., Forni, G., and Wachter, H., 1989/90, Endogenous release of interferon-gamma and diminished response of peripheral blood mononuclear cells to antigenic stimulation. Immunol. Lett. 23:103–108.PubMedCrossRefGoogle Scholar
  7. Fuchs, D., Möller, A.A., Reibnegger, G., Stöckle, E., Werner, E.R., and Wachter H., 1990, Decreased serum tryptophan in patients with HIV-1 infection correlates with increased serum neopterin and with neurologic/psychiatric symptoms. J. Acquir. Immune Defic. Syndr. 3:873–876.PubMedGoogle Scholar
  8. Fuchs, D., Weiss, G., and Wachter, H., 1993, Neopterin, biochemistry and clinical use as a marker for cellular immune reactions, Int. Arch. Allergy Immunol. 101:1–6.PubMedCrossRefGoogle Scholar
  9. Gasse, T., Widner, B., Baier-Bitterlich, G., Sperner-Unterweger, B., Leblhuber, B., Wachter, H., and Fuchs, D., 1998, Abnormal tryptophan metabolism, neurologic/psychiatric disturbances and its relationship to immune activation, in: Progress in HPLC-HPCE: Vol. 7. Neurochemical markers of degenerative diseases and drug addiction, (G.A. Qureshi, H. Parvez, P. Caudy, and S. Parvez, eds), pp. 351–381, VSP Püress, Zeit.Google Scholar
  10. Hagberg, L., Dotevall, L., Norkrans, G., Larsson, M., Wachter, H., and Fuchs, D., 1993, Cerebrospinal fluid neopterin concentrations in central nervous system infection. J. Infect. Dis. 168:1285–1288.PubMedCrossRefGoogle Scholar
  11. Hampel, H., Muller-Spahn, F, Berger, C., Haberl, A., Ackenheil, M., and Hoch, C., 1995, Evidence of blood-cerebrospinal fluid impairment in a subgroup of patients with dementia of the Alzheimer type and major depression: a possible indicator for immunoactivation, Dementia 6:348–354.PubMedGoogle Scholar
  12. Heyes, M.P., Saito, K., Crowley, J.S., Davies, L.E., Demitrack, M.A., Dez, M., Diling, L.A., Elia, J., Kruesi, M.J., and Lackner, A., 1992, Quinolinic acid and kynurenine pathway metabolism in inflammatory and non-inflammatory neurological disease, Brain 115:1249–1273.PubMedCrossRefGoogle Scholar
  13. Jenner, P., 1994, Oxidative damage in neurodegenerative disease, Lancet 344:796–798.PubMedCrossRefGoogle Scholar
  14. Leblhuber, F., Walli, J., Tilz, G.P., Jellinger, K., Wachter, H., and Fuchs, D., 1996, Increased serum neopterin concentrations in a patient with Creutzfeld-Jacob disease, J. Neurol. Neurosurg. Psych. 10:138–139.Google Scholar
  15. Leblhuber, F., Walli, J., Jellinger, K., Tilz, G.P., Widner, B., Laccone, F., and Fuchs, D., 1998, Activated immune system in patients with Huntington’s disease, Clin. Chem. Lab. Immunol. 36:747–740.Google Scholar
  16. Leblhuber, F., Walli, J., Tilz, G.P., Demel, U., Widner, B., and Fuchs, D., Activated immune system in patients with Alzheimer’s disease, Clin. Chem. Lab. Immunol. (in press).Google Scholar
  17. Martin, J.B., 1984, Huntington’s disease: new approaches to an old problem. Neurology 34:1059–1072.PubMedCrossRefGoogle Scholar
  18. Rich, B.J., Rasmusson, D.X., Folstein, N.F., Carson, R.A., Kawas, C., and Brandt, J., 1995, Nonsteroidal anti-inflammatory drugs in Alzheimer’s disease, Neurology 45:51–55.PubMedCrossRefGoogle Scholar
  19. Rogers, J., Webster, S., Lue, L.F., Brachova, L., Civin, W.H., Emmerling, M., Shivers, B., Walker, D., and McGeer, P., 1996, Inflammation and Alzheimer’s disease pathogenesis. Neurobiol. Ageing 17:681–686.CrossRefGoogle Scholar
  20. Schwarcz, R., Tamminga, C.A., Kurlan, R., and Shoulson, I., 1988, Cerebrospinal fluid levels of quinolinic acid in Huntington’s disease and Schizophrenia. Ann. Neurol. 24:580–582.PubMedCrossRefGoogle Scholar
  21. Shahabuddin, S., 1991, Expression and release of IL-2 receptor and production of IL-2 by activated T-lymphocyte subsets, J. Clin. Lab. Immunol. 36:27–32.PubMedGoogle Scholar
  22. Shalit, F, Sredni, B., Brodie, C., Kott, E., and Huberman, M.T., 1995, Lymphocyte subpopulations and activation markers correlate with severity of Alzheimer’s disease, Clin. Immunol. Immunopathol. 75:246–250.PubMedCrossRefGoogle Scholar
  23. Singh, V.K., 1996, Immune activation model in Alzheimer disease, Mol. Chem. Neuropathol. 28:105–111.PubMedCrossRefGoogle Scholar
  24. Singh, V.K., 1997, Neuroautoimmunity: pathogenic implications for Alzheimer’s disease, Gerontology 43:79–94.PubMedCrossRefGoogle Scholar
  25. Widner, B., Werner, E.R., Schennach, H., Wachter, H., and Fuchs, D., 1997, Simultaneous measurement of serum tryptophan and kynurenine by HPLC, Clin. Chem. 43:2424–2426.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1999

Authors and Affiliations

  • B. Widner
    • 1
  • F. Leblhuber
    • 2
  • J. Walli
    • 2
  • G. P. Tilz
    • 3
  • U. Demel
    • 3
  • D. Fuchs
    • 1
  1. 1.Institute for Medical Chemistry and BiochemistryUniversity of Innsbruck, and Ludwig Boltzmann Institute of AIDS-ResearchInnsbruckAustria
  2. 2.Department for GerontologyNeurologic Clinic Wagner-JaureggLinzAustria
  3. 3.Department of Internal MedicineUniversity of GrazGrazAustria

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