Kynurenine and its metabolites in Alzheimer's disease patients

Purpose: The kynurenine pathway (KP) is a major route of tryptophan metabolism. Several metabolites of this pathway are proposed to be involved in the pathogenesis of Alzheimer's disease. The aim of this study was to evaluate peripheral KP in patients with Alzheimer type dementia and a detailed analysis of correlation between kynurenine (KYN), kynurenic acid (KYNA), 3-hydroxykynurenine (3-HK), anthranilic acid (AA), quinolinic acid (QUIN) and degree of neuropsychological changes in AD. Material/Methods: The plasma concentration of tryptophan and its products degradation by kynurenine pathway were analyzed in 34 patients suffering from Alzheimer type dementia and 18 controls in similar age using high-performance liquid chromatography technique. Results: In demented patients we found lower tryptophan and KYNA concentrations. There was a non-significant increase of KYN, 3-HK and AA levels, and a marked increase of QUIN in Alzheimer's disease group. We observed positive correlations between cognitive function tests and plasma KYNA levels, and inversely correlations between these tests and QUIN levels in Alzheimer type dementia. Conclusions: Increased TRP degradation and simultaneous altered kynurenines levels were found in plasma of AD patients. It proves activation of peripheral kynurenine pathway in this type of dementia. The alterations of two main KYN metabolites: KYNA and QUIN seem to be associated with the impairment of the cognitive function in AD patients. This appears to offer novel therapeutic opportunities, with the development of new compounds as a promising perspective for brain neuroprotection.