Elevated blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentrations in Parkinson's disease

• The environmental correlates for Parkinson's disease (PD) are unclear.
• Harmane (1-methyl-9H-pyrido[3,4-b]indole) is a potent tremor-producing toxin.
• Blood harmane levels were quantified by high performance liquid chromatography.
• Blood harmane levels were elevated in PD cases vs. controls, and highest in familial cases.
• This study provides evidence of the possible etiological importance of this toxin in PD.

BackgroundParkinson's disease (PD) is a late-life neurodegenerative disease. Genetic and environmental factors play an etiological role. Harmane (1-methyl-9H-pyrido[3,4-b]indole) is a potent tremor-producing neurotoxin that shows structural resemblance to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).ObjectivesIn 2002 and 2007, we demonstrated elevated blood harmane concentrations [HA] in essential tremor (ET) cases. We now assessed whether blood [HA] were elevated in Parkinson's disease (PD) as well.MethodsBlood [HA] were quantified by high performance liquid chromatography. Subjects comprised 113 PD cases and 101 controls.ResultsMean log blood [HA] in PD cases was double that of controls (0.59 ± 0.63 g−10/ml vs. 0.27 ± 0.63 g−10/ml, p < 0.001). A non-parametric test on non-transformed data (median blood [HA] = 3.31 g−10/ml in cases and 1.44 g−10/ml in controls) also showed this difference (p < 0.001). In unadjusted and then adjusted logistic regression analyses, log blood [HA] was associated with PD (odds ratio [OR]unadjusted 2.31, 95% confidence interval [CI] 1.46–3.67, p < 0.001; ORadjusted 2.54, 95% CI 1.55–4.16, p < 0.001). In PD, log blood [HA] co-varied with family history, being lowest in PD cases with no family history (0.54 ± 0.60 g−10/ml) and highest in PD cases with a family history of both ET and PD (0.84 ± 0.68 g−10/ml) (p = 0.06).ConclusionsBlood harmane appears to be elevated in PD. The finding needs to be reproduced in additional cohorts to assess its generalizability. The higher concentration in familial PD suggests that the mechanism may involve genetic factors.