Alterations in serum kynurenine pathway metabolites in individuals with high neocortical amyloid-β load

a pilot study

Pratishtha Chatterjee, Kathryn Goozee, Chai K. Lim, Ian James, Kaikai Shen, Kelly R. Jacobs, Hamid R. Sohrabi, Tejal Shah, Prita R. Asih, Preeti Dave, Candice ManYan, Kevin Taddei, David B. Lovejoy, Roger Chung, Gilles J. Guillemin, Ralph N. Martins*

*Corresponding author for this work

Research output: Contribution to journalArticle

12 Citations (Scopus)
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Abstract

The kynurenine pathway (KP) is dysregulated in neuroinflammatory diseases including Alzheimer's disease (AD), however has not been investigated in preclinical AD characterized by high neocortical amyloid-β load (NAL), prior to cognitive impairment. Serum KP metabolites were measured in the cognitively normal KARVIAH cohort. Participants, aged 65-90y, were categorised into NAL+ (n = 35) and NAL- (n = 65) using a standard uptake value ratio cut-off = 1.35. Employing linear models adjusting for age and APOEϵ4, higher kynurenine and anthranilic acid (AA) in NAL+ versus NAL- participants were observed in females (kynurenine, p = 0.004; AA, p = 0.001) but not males (NALxGender, p = 0.001, 0.038, respectively). To evaluate the predictive potential of kynurenine or/and AA for NAL+ in females, logistic regressions with NAL+/- as outcome were carried out. After age and APOEϵ4 adjustment, kynurenine and AA were individually and jointly significant predictors (p = 0.007, 0.005, 0.0004, respectively). Areas under the receiver operating characteristic curves were 0.794 using age and APOEϵ4 as predictors, and 0.844, 0.866 and 0.871 when kynurenine, AA and both were added. Findings from the current study exhibit increased KP activation in NAL+ females and highlight the predictive potential of KP metabolites, AA and kynurenine, for NAL+. Additionally, the current study also provides insight into he influence of gender in AD pathogenesis.

Original languageEnglish
Article number8008
Pages (from-to)1-10
Number of pages10
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - 1 Dec 2018

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Copyright the Author(s) 2018. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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