title: Elevated blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentrations in Parkinson's disease.
abstract: 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).
  
  
  OBJECTIVE
  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±0.63 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; 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±0.60 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).
  
  
  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.
authors.affiliation: GH Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA. Electronic address: EDL2@columbia.edu.
authors.forename: Elan D
authors.initials: ED
authors.lastname: Louis
authors.affiliation: GH Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA. Electronic address: mg3360@cumc.columbia.edu.
authors.forename: Monika
authors.initials: M
authors.lastname: Michalec
authors.affiliation: Purdue University School of Health Sciences, West Lafayette, IN, USA. Electronic address: jiangw@purdue.edu.
authors.forename: Wendy
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA. Electronic address: prf1@cumc.columbia.edu.
authors.forename: Pam
authors.initials: P
authors.lastname: Factor-Litvak
authors.affiliation: Purdue University School of Health Sciences, West Lafayette, IN, USA. Electronic address: wzheng@purdue.edu.
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
mesh_terms: D000368:Aged; D005260:Female; D006247:Harmine / Q000031:analogs & derivatives* / Q000097:blood; D006801:Humans; D008297:Male; D009498:Neurotoxins / Q000097:blood*; D010300:Parkinson Disease / Q000097:blood*; D012307:Risk Factors
chemical_list: D009498:Neurotoxins; D006247:Harmine; C005010:harman
keywords: Parkinson's disease; beta-carboline alkaloid; environmental risk factors; epidemiology; harmane