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

Background: Parkinson'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). Objectives: In 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. Methods: Blood [HA] were quantified by high performance liquid chromatography. Subjects comprised 113 PD cases and 101 controls. Results: Mean log blood [HA] in PD cases was double that of controls (0.59±0.63g^-10/ml vs. 0.27±0.63g^-10/ml, p<0.001). A non-parametric test on non-transformed data (median blood [HA]=3.31g^-10/ml in cases and 1.44g^-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; OR_adjusted 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±0.60g^-10/ml) and highest in PD cases with a family history of both ET and PD (0.84±0.68g^-10/ml) (p=0.06). Conclusions: Blood 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.