Increased 3-Hydroxykynurenine serum concentrations differentiate Alzheimer's disease patients from controls

Markus J. Schwarz*, Gilles J. Guillemin, Stefan J. Teipel, Katharina Buerger, Harald Hampel

*Corresponding author for this work

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

Increased degradation of tryptophan (TRP) through the kynurenine (KYN) pathway (KP) is known to be involved in the molecular mechanisms resulting in the neuropathogenesis of Alzheimer's disease (AD). Activation of the KP leads to the production of neurotoxic metabolites 3-hydroxykynurenine (3-HK) and quinolinic acid (QUIN) by immune cells and neuroprotective derivates kynurenic acid (KYNA) and picolinic acid (PIC) by astrocytes and neurons. We therefore investigated whether an imbalance between neurotoxic and neuroprotective kynurenine metabolites could be detected in patients with AD. We measured serum levels of TRP, KYNA, 3-HK, PIC and QUIN in 20 patients with AD and for comparison in 20 patients with major depression, and 19 subjectively cognitive impaired subjects. Serum levels of 3-HK were markedly increased in AD patients compared to the comparison groups (p <.0001). Serum levels of the other KP metabolites were not significantly different between groups. Our data indicate an increased production of the neurotoxic KP metabolite 3-HK in AD. In contrast to its downstream metabolites QUIN and PIC, 3-HK can cross the blood-brain barrier via an active transport process. Our data therefore indicate an enhanced availability of 3-HK in the brain of AD patients, which may be related to the previously reported higher production of QUIN in AD brains.

Original languageEnglish
Pages (from-to)345-352
Number of pages8
JournalEuropean Archives of Psychiatry and Clinical Neuroscience
Volume263
Issue number4
DOIs
Publication statusPublished - Jun 2013
Externally publishedYes

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