Kynurenine Pathway Metabolites in Alzheimer's Disease

Metabolites of tryptophan, produced via the kynurenine pathway (kynurenines), have been linked to Alzheimer's disease (AD) in small cohorts with conflicting results. To compare differences in plasma kynurenine levels between AD and controls and identify potential associations with cognition. Th...

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Veröffentlicht in:Journal of Alzheimer's disease Jg. 60; H. 2; S. 495
Hauptverfasser: Giil, Lasse Melvaer, Midttun, Øivind, Refsum, Helga, Ulvik, Arve, Advani, Rajiv, Smith, A David, Ueland, Per Magne
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Netherlands 01.01.2017
Schlagworte:
3-Hydroxyanthranilic Acid - metabolism
Aged
Aged, 80 and over
Aging - blood
Alzheimer Disease - blood
Cognition Disorders - etiology
Cohort Studies
Female
Humans
Kynurenine - blood
Male
Middle Aged
Neuropsychological Tests
Quinolinic Acid - blood
Signal Transduction - physiology
Statistics, Nonparametric
Tryptophan - blood
Xanthurenates - blood
kynurenine pathway
Alzheimer’s disease
cognition
xanthurenic acid
quinolinic acid
vitamin B6
dementia
aging
ISSN:1875-8908, 1875-8908
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Zusammenfassung:Metabolites of tryptophan, produced via the kynurenine pathway (kynurenines), have been linked to Alzheimer's disease (AD) in small cohorts with conflicting results. To compare differences in plasma kynurenine levels between AD and controls and identify potential associations with cognition. The study included 65 histopathologically-confirmed AD patients and 65 cognitively-screened controls from the Oxford Project to Investigate Memory and Ageing (OPTIMA) cohort. Cognition was assessed using the Cambridge Cognitive Examination (CamCog). Tryptophan, kynurenines, neopterin, and vitamin B6 forms were measured in plasma by liquid chromatography-tandem mass spectrometry. Non-parametric statistics, logistic regression and standardized robust regressions were applied with a false discovery rate of 0.05. Tryptophan, xanthurenic acid, 3-hydroxyanthranilic acid, and quinolinic acid were lower in AD (Odds ratios (ORs) 0.24 -0.47; p-values <0.001 -0.01). Pyridoxal 5'phosphate did not differ between AD and controls. Kynurenine, anthranilic acid, quinolinic acid, and markers of immune activation (neopterin, kynurenine/tryptophan ratio, and the PAr index (Pyridoxic acid/(Pyridoxal 5'phosphate + Pyridoxal)) increased with age (β 0.31 -0.51; p-values <0.001 -0.006). Xanthurenic acid decreased with age (β: -0.42, p < 0.001). Elderly AD patients with high quinolinic acid performed worse on the CamCog test, indicated by a significant age*quinolinic acid interaction (β 0.21, p < 0.001). Plasma concentrations of several kynurenines were lower in patients with AD compared to controls. Low xanthurenic acid occurred in both AD and with aging. Inflammation-related markers were associated with age, but not AD. However, elevated QA was associated with poor cognition in older AD patients.
Bibliographie:ObjectType-Article-1
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ISSN:1875-8908
1875-8908
DOI:10.3233/JAD-170485