Journal Article

DZNE-2020-03251

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Increased 3-hydroxykynurenine serum concentrations differentiate Alzheimer's disease patients from controls.

Schwarz, M. J. (Corresponding author) ; Guillemin, G. J. ; Teipel, S. J.DZNE* ; Buerger, K. ; Hampel, H.

2013
Springer Heidelberg

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Please use a persistent id in citations: doi:10.1007/s00406-012-0384-x

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.

Keyword(s): Aged (MeSH) ; Alzheimer Disease: blood (MeSH) ; Alzheimer Disease: psychology (MeSH) ; Biomarkers: blood (MeSH) ; Blood-Brain Barrier (MeSH) ; Brain Chemistry: physiology (MeSH) ; Chromatography, High Pressure Liquid (MeSH) ; Cognition Disorders: blood (MeSH) ; Cognition Disorders: psychology (MeSH) ; Female (MeSH) ; Gas Chromatography-Mass Spectrometry (MeSH) ; Humans (MeSH) ; Kynurenic Acid: blood (MeSH) ; Kynurenic Acid: metabolism (MeSH) ; Kynurenine: analogs & derivatives (MeSH) ; Kynurenine: blood (MeSH) ; Male (MeSH) ; Neuropsychological Tests (MeSH) ; Picolinic Acids: blood (MeSH) ; Picolinic Acids: metabolism (MeSH) ; Quinolinic Acid: blood (MeSH) ; Spectrophotometry, Ultraviolet (MeSH) ; Tryptophan: metabolism (MeSH) ; Biomarkers ; Picolinic Acids ; 3-hydroxykynurenine ; Kynurenine ; Tryptophan ; Quinolinic Acid ; Kynurenic Acid ; picolinic acid

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Contributing Institute(s):

1. Clinical Dementia Research (Rostock /Greifswald) (AG Teipel)

Research Program(s):

1. 344 - Clinical and Health Care Research (POF3-344) (POF3-344)

Appears in the scientific report 2013

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Database coverage:
; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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