Alterations in serum kynurenine pathway metabolites in individuals with high neocortical amyloid-beta load: A pilot study

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

来源：Scientific Reports, 2018, 8(1): 8008.

DOI：10.1038/s41598-018-25968-7

• PRECLINICAL ALZHEIMERS-DISEASE
• MONTREAL COGNITIVE ASSESSMENT
• INDOLEAMINE 2,3 DIOXYGENASE
• TRYPTOPHAN-METABOLISM
• QUINOLINIC ACID
• IMMUNE ACTIVATION
• 2,3-DIOXYGENASE
• DEMENTIA
• ESTROGEN
• CELLS

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.

• 出版日期2018-5-22
• 单位CSIRO