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

Kelly Jacobs, Chai K. Lim, Kaj Blennow, Henrik Zetterberg, Pratishtha Chatterjee, Ralph N. Martins, Bruce Brew, Gilles Guillemin, David Lovejoy*

*Corresponding author for this work

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)11-20
Number of pages10
JournalNeurobiology of Aging
Volume80
DOIs
Publication statusPublished - 1 Aug 2019

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Keywords

  • Alzheimer's disease
  • Amyloid-β
  • Cerebrospinal fluid
  • Disease biomarkers
  • Kynurenine pathway
  • Tau protein

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