title: Increased 3-hydroxykynurenine serum concentrations differentiate Alzheimer's disease patients from controls.
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.
authors.affiliation: Institute for Laboratory Medicine, University of Munich, Nussbaumstr. 7, 80336 Munich, Germany. Markus.Schwarz@med.uni-muenchen.de
authors.forename: Markus J
authors.initials: MJ
authors.lastname: Schwarz
authors.forename: Gilles J
authors.initials: GJ
authors.lastname: Guillemin
authors.forename: Stefan J
authors.initials: SJ
authors.lastname: Teipel
authors.forename: Katharina
authors.initials: K
authors.lastname: Buerger
authors.forename: Harald
authors.initials: H
authors.lastname: Hampel
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000097:blood* / Q000523:psychology; D015415:Biomarkers / Q000097:blood; D001812:Blood-Brain Barrier; D001923:Brain Chemistry / Q000502:physiology; D002851:Chromatography, High Pressure Liquid; D003072:Cognition Disorders / Q000097:blood / Q000523:psychology; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007736:Kynurenic Acid / Q000097:blood / Q000378:metabolism; D007737:Kynurenine / Q000031:analogs & derivatives* / Q000097:blood; D008297:Male; D009483:Neuropsychological Tests; D010848:Picolinic Acids / Q000097:blood / Q000378:metabolism; D017378:Quinolinic Acid / Q000097:blood; D013056:Spectrophotometry, Ultraviolet; D014364:Tryptophan / Q000378:metabolism
chemical_list: D015415:Biomarkers; D010848:Picolinic Acids; C005045:3-hydroxykynurenine; D007737:Kynurenine; D014364:Tryptophan; D017378:Quinolinic Acid; D007736:Kynurenic Acid; C030614:picolinic acid