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To investigate the significance of nitric oxide (NO)-mediated neuron death in aging and Alzheimer's disease (AD), the 3-nitrotyrosine concentration in the cerebrospinal fluid (CSF) was investigated in neurologically normal controls and patients with AD. The 3-nitrotyrosine concentration and the 3-nitrotyrosine/tyrosine ratio significantly increased with advancing age, whereas the tyrosine concentration was unaltered. In patients with AD, the 3-nitrotyrosine concentration and the 3-nitrotyrosine/tyrosine ratio increased significantly (>six-fold) compared with controls of similar age, and increased significantly with decreasing cognitive functions, whereas the tyrosine concentration did not change. These findings suggest that an activation of tyrosine nitration, increase in nitrated tyrosine-containing proteins, and/or its degradation may be involved in brain aging and play an important role in the pathogenesis of AD.

We compared the concentrations of dopaminergic substances in the plasma and cerebrospinal fluid (CSF) with clinical severity in patients with Parkinson's disease (PD) under L-dopa/carbidopa treatment and under L-dopa/carbidopa+tolcapone treatment. Compared with treatment with L-dopa/carbidopa alone, the co-administration of tolcapone produced a significant decrease in clinical severity; a remarkable reduction in the 3-O-methyldopa (3-OMD) concentration and significant increase in the L-dopa concentration both in the plasma and CSF; and a significant increase in the dopamine concentration in the CSF. The clinical effects of tolcapone were closely correlated with the reduction in the 3-OMD concentration, but not with the increase in the dopamine and L-dopa concentrations in the CSF.

We determined concentrations of 3-O-methyldopa (3-OMD), L-3,4-dihydroxyphenylalanine (L-dopa), dopamine (DA) and other related substances in the cerebrospinal fluid in patients with Parkinson's disease (PD) 15 h after L-dopa/carbidopa medication, and compared patients with and without the wearing-off phenomenon. Concentrations of 3-OMD significantly increased, and the ratio of DA to 3-OMD was significantly shifted in favor of 3-OMD in patients with the wearing-off compared with patients without the wearing-off. However, concentrations of L-dopa, DA, and homovanillic acid (HVA) were not different between the groups. These results suggest that even if 3-OMD is related to the pathogenesis of the wearing-off, it is not through competition with L-dopa for uptake into the brain, but through other unknown mechanisms within the brain.

We determined the concentrations of tyrosine, L-3,4-dihydroxyphenylalanine (DOPA), dopamine (DA), and 3-O-methyldopa (3-OMD) in the cerebrospinal fluid (CSF) of parkinsonian patients and elevated potential interactions between the substances. We found a significant increase in tyrosine, and a significant decrease in DOPA, DA, and 3-OMD. We also found that for a given concentration of DOPA, DA and 3-OMD were proportional. In addition, the ratio of DA to 3-OMD was significantly shifted in favor of DA in parkinsonian patients.