Title

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

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

Grant Number

NHMRC Number : 1128849

Comments

Originally published as: 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. Original publication 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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