The Associations Between Cognitive Prognosis and Kynurenines Are Modified by the Apolipoprotein ?4 Allele Variant in Patients With Dementia.

ABSTRACT: Background:The apolipoprotein E ?4 gene variant (APOE?4) confers considerable risk for dementia and affects neuroinflammation, brain metabolism, and synaptic function. The kynurenine pathway (KP) gives rise to neuroactive metabolites, which have inflammatory, redox, and excitotoxic effects in the brain. Aim:To assess whether the presence of at least one APOE?4 allele modifies the association between kynurenines and the cognitive prognosis. Methods:A total of 152 patients with sera for metabolite measurements and APOE genotype were included from the Dementia Study of Western Norway. The participants had mild Alzheimer disease and Lewy body dementia. Apolipoprotein E ?4 gene variant allele status was classified as one or more ?4 versus any other. Mini-Mental State Examination (MMSE) was measured at baseline and for 5 consecutive years. Mann-Whitney U tests and linear mixed-effects models were used for statistical analysis. Results:There were no significant differences in serum concentrations of tryptophan and kynurenine according to the presence or absence of APOE?4. High serum concentrations of kynurenic acid, quinolinic acid, and picolinic acid, and a higher kynurenine-to-tryptophan ratio, were all associated with more cognitive decline in patients without APOE?4 compared to those with the APOE?4 allele (P-value of the interactions?

SUBMITTER: Ervik AO 

PROVIDER: S-EPMC6859685 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature