TY - JOUR
T1 - Alterations in serum kynurenine pathway metabolites in individuals with high neocortical amyloid-β load
T2 - A pilot study
AU - Chatterjee, Pratishtha
AU - Goozee, Kathryn
AU - Lim, Chai K.
AU - James, Ian
AU - Shen, Kaikai
AU - Jacobs, Kelly R.
AU - Sohrabi, Hamid R.
AU - Shah, Tejal
AU - Asih, Prita R.
AU - Dave, Preeti
AU - Man Yan, Candice
AU - Taddei, Kevin
AU - Lovejoy, David B.
AU - Chung, Roger
AU - Guillemin, Gilles J.
AU - Martins, Ralph N.
PY - 2018/5/22
Y1 - 2018/5/22
N2 - 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 65-90 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 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.
AB - 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 65-90 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 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.
KW - kynurenine pathway (KP)
KW - Alzheimer's disease (AD)
KW - neocortical amyloid-β load (NAL)
KW - Serum KP metabolites
KW - KARVIAH cohort
KW - AD pathogenesis
UR - http://www.scopus.com/inward/record.url?scp=85047633789&partnerID=8YFLogxK
U2 - 10.1038/s41598-018-25968-7
DO - 10.1038/s41598-018-25968-7
M3 - Article
SN - 2045-2322
VL - 8
JO - Scientific Reports
JF - Scientific Reports
M1 - 8008
ER -