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SHR Neuro Cancer Cardio Lipid Metab Microb

Greilberger, J; Fuchs, D; Leblhuber, F; Greilberger, M; Wintersteiger, R; Tafeit, E.
Carbonyl proteins as a clinical marker in Alzheimer's disease and its relation to tryptophan degradation and immune activation.
Clin Lab. 2010; 56(9-10): 441-448.
Web of Science PubMed

Leading authors Med Uni Graz: Greilberger Joachim
Co-authors Med Uni Graz: Tafeit Erwin
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Abstract:: Background: The question arises whether oxidative stress is connected with systemic immune activation in Alzheimer's disease (AD) and mild cognitive impairment (MCI). During immune response interferon-gamma stimulates the kynurenine (Kyn) pathway, a major route of L-tryptophan (Trp) degradation. Methods: Plasma Kyn, Trp and the Kyn to Trp ratio (Kyn/Trp), carbonyl proteins (CP) as oxidative stress parameter and homocysteine, neopterin, folate and vitamin B12 were measured from patients with AD and MCI (n = 16: 6 females and 4 males with AD, 3 females and 3 males with MCI; 63.3 +/- 13.7 years), and an age matched healthy control group (n = 15: 11 females and 4 males; 62.8 +/- 3.6 years). We correlated the oxidative stress parameter CP with the degradation of Trp creating a new quotient CP/Trp and calculated the sensitivity, specificity, and cut-off values for CP, Trp, CP/Trp, and Kyn/Trp using discriminate analysis. Results: CP was significantly higher in AD/MCI (930 +/- 265 pmol/mg; p < 0.001) compared to controls (300 +/- 120 pmol/mg), Trp was significantly lower in AD/MCI (48.9 +/- 9.0 mu mol/L; p < 0.001) than controls (65.2 +/- 10.7 mu mol/L). While Kyn showed no significant difference between AD/MCI (1.72 +/- 0.56 mu mol/L) and controls (1.53 +/- 0.29 mu mol/L), Kyn/Trp was significantly higher in AD/MCI (35.2 +/- 8.8 mu mol/mmol; p < 0.001) than in controls (23.7 +/- 4.2 mu mol/mmol). CP/Trp ratio was more than 4 fold higher in the AD/MCI group (19.8 +/- 7.76 [(pmol/mg)/(mu mol/L)]; p < 0.001) compared to controls (4.79 +/- 2.26 [(pmol/mg)/(mu mol/L)]). Homocysteine, folate, vitamin B12, and neopterin showed no significant difference. Discriminant analysis provided CP alone as the best clinical marker with highest sensitivity and highest specificity for AD/MCI followed by the ratio of CP/Trp. ROC curve analysis provided the best result for CP/Trp. Conclusions: These preliminary results support the hypothesis that oxidative damage to proteins is directly connected with Trp degradation and Kyn pathway in the systemic immune activation. (Clin. Lab. 2010;56:441-448)
Find related publications in this database (using NLM MeSH Indexing): Aged -; Alzheimer Disease - blood; Biological Markers - blood; Cognition Disorders - blood; Female -; Folic Acid - blood; Homocysteine - blood; Humans -; Male -; Middle Aged -; Neopterin - blood; Oxidative Stress -; Protein Carbonylation - physiology; Reference Values -; Tryptophan - immunology; Vitamin B 12 - blood
Find related publications in this database (Keywords): Alzheimer's disease (AD); carbonyl proteins (CP); kynurenine (Kyn); mild cognitive impairment (MCI); receiver operating characteristic (ROC); tryptophan (Trp)