Journal
SCIENTIFIC REPORTS
Volume 8, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-018-25968-7
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Funding
- Foundation of Aged Care, Anglicare, Sydney
- Australian Alzheimer Research Foundation (AARF), Perth
- KaRa Institute of Neurological Diseases (KaRa MINDs), Sydney
- Cooperative Research Centre for Mental Health top-up scholarship
- National Health and Medical Research Council (NHMRC)
- Australian Research Council (ARC)
- Macquarie University
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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-beta load (NAL), prior to cognitive impairment. Serum KP metabolites were measured in the cognitively normal KARVIAH cohort. Participants, aged 65-90 y, 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 APOE epsilon 4, 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 APOE epsilon 4 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 APOE epsilon 4 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.
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