Output list
Conference poster
Published 2018
Alzheimer's & Dementi, 14, 7S Pt.14, P789
The Alzheimer's Association International Conference (AAIC2018) 2018, 22/07/2018–26/07/2018, Chicago, Illinois
Background
The kynurenine pathway (KP), generating the essential co-factor nicotinamide adenine dinucleotide, is dysregulated in several neurodegenerative and neuropsychiatric disorders including Alzheimer's disease (AD). However, alterations in the KP have not been investigated in the preclinical phase of AD, characterized by high neocortical amyloid-β load (NAL), prior to cognitive impairment.
Methods
Serum concentrations of KP metabolites including tryptophan, kynurenine, 3-hydroxykynurenine, anthranilic acid, 3-hydroxyanthranilic acid, picolinic acid and quinolinic acid were measured using UHPLC and GCMS in elderly individuals, aged 65-90 years, with normal global cognition (Mini Mental State Examination Score≥26) from the Kerr Anglican Retirement Village Initiative in Ageing Health cohort. Participants were categorised into low NAL (NAL-, n=65) and high NAL (NAL+, n=35) using a standard uptake value ratio cut-off = 1.35.
Results
Higher kynurenine (p=.0004 unadjusted, p=.004 adjusted for age and APOE ε4 carriage) and anthranilic acid (p=.0001 unadjusted, p=.001 adjusted for age and APOE ε4 carriage) concentrations in NAL+ versus NAL- participants were observed in the female subset of the cohort but not in the male subset (NAL by sex interaction p=0.001, 0.038, respectively for kynurenine and anthranilic acid). On evaluating the potential of kynurenine or/and anthranilic acid as biomarkers for NAL+ in females, logistic regressions with NAL+/- as outcome were carried out. Areas under the receiver operating characteristic curves were 0.794 using age and APOE ε4 as predictors, 0.844 when kynurenine was added, 0.866 when anthranilic acid was added, and 0.871 when both were added, such that kynurenine and anthranilic acid were individually and jointly significant predictors (p=0.007, 0.005, 0.0004, respectively).
Conclusions
Findings from the current study exhibit increased anthranilic acid and kynurenine, in NAL+ females and highlights their potential as blood biomarkers for preclinical AD. Additionally, the current study also provides insight into the influence of gender in AD pathogenesis. Further studies measuring the KP enzyme activities are underway. Additionally, longitudinal studies are required to provide further insight into the current findings.