beta-Carbolinium cations, endogenous MPP plus analogs, in the lumbar cerebrospinal fluid of patients with Parkinson's disease

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Abstract
We measured beta-carbolinium cations (BCplus s), endogenous analogs of the N-methyl-4-phenylpyridinium ion (MPPplus), in the lumbar CSF of 22 patients with idiopathic Parkinson9s disease (PD) and 11 age-matched controls without any symptoms of parkinsonism. Among the BCplus s, 2,9-dimethylnorharmanium cation (2,9-Me2 NHplus), the most potent neurotoxicant that mirrors MPPplus in mitochondria toxicity, was present in 12 patients with PD but not in controls. Although the 2-monomethylated beta-carbolinium cations (2-MeBCplus s), which were present in almost all subjects, registered a slightly higher level in PD patients than in controls, the difference was not significant. The total BCplus content, sum of 2-MeBCplus and 2,9-Me2 NHplus levels, was significantly higher in PD patients than in controls. The 2-MeBCplus contents significantly increased with the progression of the PD, but 2,9-ME2 NHplus decreased as the disease exacerbated, although levels varied within a wide range. The present results strongly support the hypothesis that ``bioactivated99 BCplus s, especially 2,9-Me2 NHplus s, may be the endogenous causative factors underlying PD. NEUROLOGY 1995;45: 2240-2245