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):441-8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / blood*
  • Alzheimer Disease / immunology
  • Alzheimer Disease / metabolism
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Cognition Disorders / blood
  • Cognition Disorders / immunology
  • Cognition Disorders / metabolism
  • Female
  • Folic Acid / blood
  • Folic Acid / metabolism
  • Homocysteine / blood
  • Homocysteine / metabolism
  • Humans
  • Male
  • Middle Aged
  • Neopterin / blood
  • Neopterin / metabolism
  • Oxidative Stress*
  • Protein Carbonylation / physiology*
  • Reference Values
  • Tryptophan / immunology
  • Tryptophan / metabolism*
  • Vitamin B 12 / blood
  • Vitamin B 12 / metabolism

Substances

  • Biomarkers
  • Homocysteine
  • Neopterin
  • Tryptophan
  • Folic Acid
  • Vitamin B 12