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

Authors

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

Author Identifier

Pratishtha Chatterjee

https://orcid.org/0000-0003-4877-1958

Ralph Martins

https://orcid.org/0000-0002-4828-9363

Document Type

Journal Article

Publication Title

Neurobiology of Aging

ISSN

1558-1497

Volume

80

First Page

11

Last Page

20

PubMed ID

31055163

Publisher

Elsevier Inc

School

School of Medical and Health Sciences

RAS ID

28907

Grant Number

NHMRC Number : 1128849

Grant Link

http://purl.org/au-research/grants/nhmrc/1128849

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

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.

DOI

10.1016/j.neurobiolaging.2019.03.015

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