Fig. 2: Vitamin B₆ deficiency associates with inflammation and neuroexcitatory KP activation in PD.

a Kynurenine pathway enzymes (blue) require B-vitamin cofactors (green) for their activity. 3-HK: 3-hydroxykynurenine, FAD flavine adenine dinucleotide, KAT kynurenine aminotransferase, KMO kynurenine 3-monooxygenase, KYNU kynureninase, PLP pyridoxal 5’phosphate. b B-vitamins, HKr, and the PAr Index in plasma from control and PD participants. HKr is a validated functional measure of vitamin B₆ status. PAr is an index of vitamin B₆ catabolism. ***P < 0.001 using ANCOVA including age and sex as covariates. HKr HK ratio. c B-vitamins and HKr in CSF from control and PD participants. HKr is a validated functional measure of vitamin B₆ status. **P < 0.01, ***P < 0.001 using ANCOVA including age and sex as covariates. HKr HK ratio. d Plasma neopterin, a validated marker of inflammation, in control and PD participants. ***P < 0.001 using ANCOVA including age and sex as covariates. e Linear regression reveals that plasma PAr is significantly correlated with plasma neopterin concentration. Age and sex were included as covariates in the linear model. Shown are the β-estimates and P-values from the linear model and the 95% confidence band of the line of best fit. PAr PAr Index. f Correlation matrix showing association between plasma metabolites (black text) and B-vitamins (blue text) in PD participants. Age and sex were included as covariates. Significant correlations are shown with the circle size indicating the P-value of the correlation and color indicating size and direction of the β-estimate. 3-HK 3-hydroxykynurenine, HKr HK ratio, Kyn kynurenine, PAr PAr Index, QA quinolinic acid. g Correlation matrix showing association between CSF metabolites (black text) and B-vitamins (blue text) in PD participants. Age and sex were included as covariates. Significant correlations are shown with the circle size indicating the P-value of the correlation and color indicating size and direction of the β-estimate. 3-HK 3-hydroxykynurenine, HKr HK ratio, Kyn kynurenine, QA quinolinic acid.