Metabolic phenotyping reveals a reduction in the bioavailability of serotonin and kynurenine pathway metabolites in both the urine and serum of individuals living with Alzheimer’s disease

Abstract Background Both serotonergic signalling disruption and systemic inflammation have been associated with the pathogenesis of Alzheimer’s disease (AD). The common denominator linking two is catabolism essential amino acid, tryptophan. Metabolism via tryptophan hydroxylase results in serotonin synthesis, whilst metabolism indoleamine 2,3-dioxygenase (IDO) kynurenine its downstream derivatives. IDO reported to be activated times host therefore thought influence both pathways. To investigate metabolic alterations AD, a large-scale phenotyping study was conducted on urine serum samples collected from multi-centre clinical cohort, consisting individuals clinically diagnosed mild cognitive impairment (MCI) age-matched controls. Methods Metabolic applied ( n = 560) 354) European-wide AddNeuroMed/Dementia Case Register (DCR) biobank repositories. Metabolite data were subsequently interrogated for inter-group differences; gender age; comparisons between subgroups MCI - versus those who remained cognitively stable at follow-up visits (sMCI); underwent further decline (cMCI); impact selective reuptake inhibitor (SSRI) medication metabolite concentrations. Results revealed significantly lower concentrations pathway metabolites AD group: (urine, serum), 5-hydroxyindoleacetic acid (urine), (serum), kynurenic xanthurenic kynurenine/tryptophan ratio (urine). For each listed metabolite, decreasing trend observed in-line diagnosis: control > AD. There no significant differences SSRI status influenced observations serum, but not urine. Conclusions Urine found compared controls, suggesting bioavailability neurotransmitter may altered disease. A increase suggests that this result shift route due increased activity, potentially as inflammation. Modulation pathways could help improve patients.