Degradation of tryptophan in neurodegenerative disorders.
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 Huntington's 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.
Widner
B
B
Institute for Medical Chemistry and Biochemistry, University of Innsbruck, Austria.
Leblhuber
F
F
Walli
J
J
Tilz
G P
GP
Demel
U
U
Fuchs
D
D
D000544:Alzheimer Disease / Q000097:blood* / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D006801:Humans; D006816:Huntington Disease / Q000097:blood* / Q000276:immunology; D008607:Intellectual Disability / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D007737:Kynurenine / Q000097:blood*; D019798:Neopterin / Q000097:blood; D015375:Receptors, Interleukin-2 / Q000097:blood; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D014364:Tryptophan / Q000097:blood* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism
D015415:Biomarkers; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D007737:Kynurenine; D019798:Neopterin; D014364:Tryptophan