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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 μmol/L; p < 0.001) than controls (65.2 ± 10.7 μmol/L). While Kyn showed no significant difference between AD/MCI (1.72 ± 0.56 μmol/L) and controls (1.53 ± 0.29 μmol/L), Kyn/Trp was significantly higher in AD/MCI (35.2 ± 8.8 μmol/mmol; p < 0.001) than in controls (23.7±4.2 μmol/mmol). CP/Trp ratio was more than 4 fold higher in the AD/MCI group (19.8 ± 7.76 [(pmol/mg)/ (μmol/L)]; p < 0.001) compared to controls (4.79 ± 2.26 [(pmol/mg)/ (μmol/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.
DOI: Clin. Lab. 2010;56:441-448
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