Age- and disease-specific changes of the kynurenine pathway in Parkinson's and Alzheimer's disease

Journal of Neurochemistry
Freek J H SorgdragerPeter P De Deyn

Abstract

The kynurenine (Kyn) pathway, which regulates neuroinflammation and N-methyl-d-aspartate receptor activation, is implicated in Parkinson's disease (PD) and Alzheimer's disease (AD). Age-related changes in Kyn metabolism and altered cerebral Kyn uptake along large neutral amino acid transporters, could contribute to these diseases. To gain further insight into the role and prognostic potential of the Kyn pathway in PD and AD, we investigated systemic and cerebral Kyn metabolite production and estimations of their transporter-mediated uptake in the brain. Kyn metabolites and large neutral amino acids were retrospectively measured in serum and cerebrospinal fluid (CSF) of clinically well-characterized PD patients (n = 33), AD patients (n = 33), and age-matched controls (n = 39) using solid-phase extraction-liquid chromatographic-tandem mass spectrometry. Aging was disease independently associated with increased Kyn, kynurenic acid and quinolinic acid in serum and CSF. Concentrations of kynurenic acid were reduced in CSF of PD and AD patients (p = 0.001; p = 0.002) but estimations of Kyn brain uptake did not differ between diseased and controls. Furthermore, serum Kyn and quinolinic acid levels strongly correlated with their respec...Continue Reading

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Citations

Feb 6, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Masaru TanakaLászló Vécsei
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Software Mentioned

GraphPad Prism
SPSS

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