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

• Published in: Neurobiology of aging Vol. 80; pp. 11 - 20
• Main Authors: Jacobs, Kelly R., Lim, Chai K., Blennow, Kaj, Zetterberg, Henrik, Chatterjee, Pratishtha, Martins, Ralph N., Brew, Bruce J., Guillemin, Gilles J., Lovejoy, David B.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2019
• Subjects: 3-dioxygenase; 3-hydroxyanthranilic acid; 3-hydroxykynurenine; Aged; Aged, 80 and over; Alzheimer Disease - etiology; Alzheimer Disease - metabolism; Alzheimer's disease; Amyloid beta-Peptides - cerebrospinal fluid; Amyloid-beta; Amyloid-β; astrocytes; brain; Cerebrospinal fluid; Disease; Disease biomarkers; Female; Geriatrics & Gerontology; human microglia; Humans; hydrogen-peroxide; indoleamine; Kynurenine - blood; Kynurenine - cerebrospinal fluid; Kynurenine pathway; Male; Neurosciences; Neurosciences & Neurology; Neurovetenskaper; quinolinate levels; Signal Transduction; Tau protein; tau Proteins - cerebrospinal fluid; tryptophan; Disease biomarkers; Amyloid-β; Cerebrospinal fluid; Tau protein; Alzheimer's disease; Kynurenine pathway
• ISSN: 0197-4580; 1558-1497; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2019.03.015

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. •CSF KP metabolites correlate with AD biomarkers, t-tau and p-tau.•Kynurenine pathway (KP) metabolites correlate in matched plasma and CSF samples.•KP correlation with t-tau and p-tau may suggest mechanistic links.