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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

Jacobs, K. R. (author)
Lim, C. K. (author)
Blennow, Kaj, 1958 (author)
Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
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Zetterberg, Henrik, 1973 (author)
Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
Chatterjee, P. (author)
Martins, R. N. (author)
Brew, B. J. (author)
Guillemin, G. J. (author)
Lovejoy, D. B. (author)
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 (creator_code:org_t)
Elsevier BV, 2019
2019
English.
In: Neurobiology of Aging. - : Elsevier BV. - 0197-4580. ; 80, s. 11-20
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Keyword

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

Publication and Content Type

ref (subject category)
art (subject category)

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