Elevated brain harmane (1-methyl-9H-pyrido[3,4-b]indole) in essential tremor cases vs. controls

Background: Harmane (1-methyl-9H-pyrido[3,4-β]indole), a potent neurotoxin that has tremor-producing properties in animal models, is present in many foods; although we have demonstrated a difference in tissue harmane concentrations in ET cases vs. controls, all work to date has involved blood samples. Objectives: We quantified harmane concentrations in human cerebellum, a brain region of particular pathogenic interest in essential tremor (ET), comparing ET to control brains. Methods: Cerebellar cortex was snap frozen and stored at -80. °C in aliquots for biochemical analyses. Harmane concentration was assessed using high performance liquid chromatography. Results: Geometric mean brain harmane concentrations (adjusted for postmortem interval [PMI] and freezer time) were higher in ET cases than controls: 1.0824 (95% confidence interval = 0.9405-1.2457) vs. 0.8037 (0.6967-0.9272), p= 0.004. Geometric mean of brain harmane concentrations (adjusting for PMI and freezer time) was highest in ET cases who reported other relatives with tremor (1.2005 [0.8712-1.6541]), intermediate in ET cases without family history (1.0312 ([0.8879-1.1976]), and both were significantly higher than controls (p= 0.02). Conclusions: This study provides additional evidence of a possible etiological importance of this toxin in some cases of the human disease ET.