Correlation between plasma and CSF concentrations of kynurenine pathway metabolites in Alzheimer's disease and relationship to amyloid-β and tau
Authors/Creators
Kelly R. Jacobs
Chai K. Lim
Kaj Blennow
Henrik Zetterberg
Pratishtha Chatterjee, Edith Cowan UniversityFollow
Ralph N. Martins, Edith Cowan UniversityFollow
Bruce J. Brew
Gilles J. Guillemin
David B. Lovejoy
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-β, 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.
Keywords
3 hydroxyanthranilic acid, 3 hydroxykynurenine, amyloid beta protein, amyloid beta protein[1-42], anthranilic acid, kynurenine, neopterin, picolinic acid, tau protein, tryptophan, aged, Alzheimer disease, Article, blood level, cerebrospinal fluid level, clinical article, controlled study, correlation analysis, enzyme linked immunosorbent assay, female, high performance liquid chromatography, human, male, mass fragmentography, pathogenesis, priority journal, protein phosphorylation, ultra performance liquid chromatography, Alzheimer's disease, Amyloid-β, Cerebrospinal fluid, Disease biomarkers, Kynurenine pathway, Tau protein
Document Type
Journal Article
Date of Publication
4-1-2019
ISSN
1558-1497
Volume
80
PubMed ID
31055163
Publication Title
Neurobiology of Aging
Publisher
Elsevier Inc
School
School of Medical and Health Sciences
RAS ID
28907
Grant Number
NHMRC Number : 1128849
Copyright
subscription content
First Page
11
Last Page
20
Comments
Jacobs, K. R., Lim, C. K., Blennow, K., Zetterberg, H., Chatterjee, P., Martins, R. N., ... & Lovejoy, D. B. (2019). Correlation between plasma and CSF concentrations of kynurenine pathway metabolites in Alzheimer's disease and relationship to amyloid-β and tau. Neurobiology of aging, 80, 11-20. Available here