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

Artikel i vetenskaplig tidskrift
Författare K. R. Jacobs
C. K. Lim
Kaj Blennow
Henrik Zetterberg
P. Chatterjee
R. N. Martins
B. J. Brew
G. J. Guillemin
D. B. Lovejoy
Publicerad i Neurobiology of Aging
Volym 80
Sidor 11-20
ISSN 0197-4580
Publiceringsår 2019
Publicerad vid Institutionen för neurovetenskap och fysiologi
Sidor 11-20
Språk en
Länkar dx.doi.org/10.1016/j.neurobiolaging...
Ämnesord Alzheimer's disease, Kynurenine pathway, Amyloid-beta, Tau protein, Cerebrospinal fluid, Disease, cerebrospinal-fluid, 3-hydroxyanthranilic acid, indoleamine, 2,3-dioxygenase, quinolinate levels, hydrogen-peroxide, human microglia, brain, 3-hydroxykynurenine, tryptophan, astrocytes, Geriatrics & Gerontology, Neurosciences & Neurology
Ämneskategorier Neurovetenskaper

Sammanfattning

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-beta, 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. (C) 2019 Published by Elsevier Inc.

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