title: Carbonyl proteins as a clinical marker in Alzheimer's disease and its relation to tryptophan degradation and immune activation.
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 micromol/L; p < 0.001) than controls (65.2 +/- 10.7 micromol/L). While Kyn showed no significant difference between AD/MCI (1.72 +/- 0.56 micromol/L) and controls (1.53 +/- 0.29 micromol/L), Kyn/Trp was significantly higher in AD/MCI (35.2 +/- 8.8 micromol/mmol; p < 0.001) than in controls (23.7 +/- 4.2 micromol/mmol). CP/Trp ratio was more than 4 fold higher in the AD/MCI group (19.8 +/- 7.76 [(pmol/mg)/(micromol/L)]; p < 0.001) compared to controls (4.79 +/- 2.26 [(pmol/mg)/(micromol/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.
authors.affiliation: Institute of Physiological Chemistry, Center for Physiological Medicine, Medical University Graz, Graz, Austria. joachim.greilberger@medunigraz.at
authors.forename: Joachim
authors.initials: J
authors.lastname: Greilberger
authors.forename: Dietmar
authors.initials: D
authors.lastname: Fuchs
authors.forename: Friedrich
authors.initials: F
authors.lastname: Leblhuber
authors.forename: Michaela
authors.initials: M
authors.lastname: Greilberger
authors.forename: Reinhold
authors.initials: R
authors.lastname: Wintersteiger
authors.forename: Erwin
authors.initials: E
authors.lastname: Tafeit
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000097:blood* / Q000276:immunology / Q000378:metabolism; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D003072:Cognition Disorders / Q000097:blood / Q000276:immunology / Q000378:metabolism; D005260:Female; D005492:Folic Acid / Q000097:blood / Q000378:metabolism; D006710:Homocysteine / Q000097:blood / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D019798:Neopterin / Q000097:blood / Q000378:metabolism; D018384:Oxidative Stress; D050050:Protein Carbonylation / Q000502:physiology*; D012016:Reference Values; D014364:Tryptophan / Q000276:immunology / Q000378:metabolism*; D014805:Vitamin B 12 / Q000097:blood / Q000378:metabolism
chemical_list: D015415:Biomarkers; D006710:Homocysteine; D019798:Neopterin; D014364:Tryptophan; D005492:Folic Acid; D014805:Vitamin B 12