Elevated 5-S-cysteinyldopamine/homovanillic acid ratio and reduced homovanillic acid in cerebrospinal fluid: possible markers for and potential insights into the pathoetiology of Parkinson's disease.
High-performance liquid chromatography with electrochemical detection has been employed to analyze ultrafiltrates of cerebrospinal fluid of Parkinson's Disease (PD) patients and age-matched controls for the dopamine (DA) metabolites homovanillic acid (HVA) and 5-S-cysteinyldopamine (5-S-CyS-DA). The mean level of HVA in the CSF of PD patients, measured 5 days after withdrawal from L-DOPA therapy, was significantly lower than that measured in controls. By contrast, mean levels of 5-S-CyS-DA were not significantly different in the CSF of PD patients taking L-DOPA (PD-LT patients) the same patients 5 days after discontinuing this drug (PD-LW patients) or controls. However, the mean 5-S-CyS-DA/HVA concentration ratio was significantly (p < 0.05) higher in the CSF of PD-LW patients compared to controls. Although the PD patient population employed in this study had been diagnosed with the disease several years previously and had been treated with L-DOPA for prolonged periods of time the results of this study suggest that low CSF levels of HVA and a high 5-S-CyS-DA/HVA ratio together might represent useful markers for early diagnosis of PD. The high 5-S-CyS-DA/HVA ratio observed in the CSF of PD-LW patients also provides support for the hypothesis that the translocation of glutathione or L-cysteine into neuromelanin-pigmented dopaminergic cell bodies in the substantia nigra might represent an early event in the pathogenesis of PD.
Cheng
F C
FC
Department of Medical Research and Geriatrics Medical Center, Taichung, Taiwan, Republic of China.
Kuo
J S
JS
Chia
L G
LG
Dryhurst
G
G
D000368:Aged; D000978:Antiparkinson Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000031:analogs & derivatives* / Q000134:cerebrospinal fluid; D005260:Female; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid*; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D008297:Male; D010300:Parkinson Disease / Q000134:cerebrospinal fluid* / Q000188:drug therapy / Q000503:physiopathology; D012016:Reference Values
D000978:Antiparkinson Agents; D015415:Biomarkers; D007980:Levodopa; C047408:5-S-cysteinyldopamine; D004298:Dopamine; D006719:Homovanillic Acid