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Correlation between plasma and CSF concentrations of kynurenine pathway metabolites in Alzheimer's disease and relationship to amyloid-beta and tau

Journal article
Authors K. R. Jacobs
C. K. Lim
Kaj Blennow
Henrik Zetterberg
P. Chatterjee
R. N. Martins
B. J. Brew
G. J. Guillemin
D. B. Lovejoy
Published in Neurobiology of Aging
Volume 80
Pages 11-20
ISSN 0197-4580
Publication year 2019
Published at Institute of Neuroscience and Physiology
Pages 11-20
Language en
Links dx.doi.org/10.1016/j.neurobiolaging...
Keywords Alzheimer's disease, Kynurenine pathway, Amyloid-beta, Tau protein, Cerebrospinal fluid, Disease, cerebrospinal-fluid, 3-hydroxyanthranilic acid, indoleamine, 2,3-dioxygenase, quinolinate levels, hydrogen-peroxide, human microglia, brain, 3-hydroxykynurenine, tryptophan, astrocytes, Geriatrics & Gerontology, Neurosciences & Neurology
Subject categories Neurosciences

Abstract

Chronic kynurenine pathway (KP) activation is implicated in Alzheimer's disease (AD) pathophysiology and results in quinolinic acid-induced excitotoxic stimulation of the N-methyl-D-aspartate receptor. However, most studies focus on plasma and it is unclear if peripheral concentrations reflect brain concentrations and how these may correlate to the AD biomarkers amyloid-beta, total-tau (t-tau), or phosphorylated-tau (p-tau). We characterized the KP in matched plasma and cerebrospinal fluid (CSF) samples from 20 AD patients and 18 age-matched control subjects. Plasma concentrations of kynurenine (KYN), 3-hydroxykynurenine, anthranilic acid, picolinic acid, and neopterin significantly correlated with their respective CSF levels. In patients with AD, plasma KYN (r = -0.48, p = 0.033) and picolinic acid (r = -0.57, p = 0.009) inversely correlated with CSF p-tau and t-tau, respectively. Furthermore, in AD CSF, increased 3-hydroxykynurenine/KYN ratio correlated with t-tau (r = 0.58, p = 0.009) and p-tau (r = 0.52, p = 0.020). These data support KP involvement in AD pathogenesis and add to the case for the therapeutic modulation of the KP in AD. (C) 2019 Published by Elsevier Inc.

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