Jenner P
Parkinson's Disease Society Experimental Research Laboratories, King's College, London, United Kingdom.
J Neural Transm Suppl. 1993;40:23-36.
Presymptomatic detection of Parkinson's disease is necessary if neuroprotective therapies are to be utilized in its treatment. Various methods (PET, electrophysiology, enzyme assays, olfactory function) may be applicable but none has been rigorously evaluated. Other possible approaches are now considered. Plasma HVA levels (pHVA) in the presence of debrisoquine may reflect cerebral dopamine function. However, there are no detectable differences in pHVA between newly diagnosed and untreated parkinsonian patients and control subjects. Compensatory increases in dopamine turnover may mask a decrease in pHVA in the early stages of the disease. So, at present this technique could not be used as a diagnostic tool. Post-mortem studies of brain in Parkinson's disease may provide clues to biochemical markers indicative of nigral pathology. Mitochondrial complex I activity is reduced in substantia nigra in Parkinson's disease and it was reported also to be markedly reduced in blood platelets. However, subsequent studies suggest that the difference in platelet complex I activity is too small to be diagnostic of Parkinson's disease. There are also selective reductions in brain glutathione levels in Parkinson's disease restricted to substantia nigra, which do not occur in other neurodegenerative disorders and are not due to drug treatment. Importantly, in incidental Lewy body disease (preclinical Parkinson's disease) nigral glutathione levels are reduced to the same degree as in advanced Parkinson's disease. So, some peripheral index of altered glutathione function may be valuable in the early detection of the disease process.
如果要在帕金森病的治疗中使用神经保护疗法，对其进行症状前检测是必要的。各种方法（正电子发射断层扫描、电生理学、酶测定、嗅觉功能）可能适用，但尚未经过严格评估。现在考虑其他可能的方法。在存在异喹胍的情况下，血浆高香草酸水平（pHVA）可能反映脑多巴胺功能。然而，新诊断且未治疗的帕金森病患者与对照受试者之间的pHVA没有可检测到的差异。多巴胺周转率的代偿性增加可能掩盖疾病早期pHVA的降低。因此，目前这项技术不能用作诊断工具。帕金森病患者大脑的尸检研究可能为指示黑质病理的生化标志物提供线索。帕金森病患者黑质中的线粒体复合体I活性降低，据报道血小板中的该活性也明显降低。然而，随后的研究表明，血小板复合体I活性的差异太小，无法诊断帕金森病。帕金森病患者大脑中谷胱甘肽水平也有选择性降低，仅限于黑质，在其他神经退行性疾病中不会出现，也不是药物治疗所致。重要的是，在偶发性路易体病（临床前帕金森病）中，黑质谷胱甘肽水平降低到与晚期帕金森病相同的程度。因此，谷胱甘肽功能改变的一些外周指标可能对疾病进程的早期检测有价值。
