PDF(Pubmed)
Abstract：
The fact that Parkinson\'s disease (PD) pathologies are well advanced in most PD patients by the time of clinical elucidation attests to the importance of early diagnosis. Our attempt to achieve this has capitalized on our previous finding that GM1 ganglioside is expressed at subnormal levels in virtually all tissues of sporadic PD (sPD) patients including blood cells. GM1 is present in most vertebrate cells, is especially abundant in neurons where it was shown essential for their effective functioning and long term viability. We have utilized peripheral blood mononuclear cells (PBMCs) which, despite their low GM1, we found to be significantly lower in sPD patients compared to age-matched healthy controls. To quantify GM1 (and GD1a) we used high performance thin-layer chromatography combined with cholera toxin B linked to horseradish peroxidase, followed by densitometric quantification. GM1 was also deficient in PBMCs from PD patients with mutations in the glucocerebrosidase gene (PD-GBA), apparently even lower than in sPD. Reasons are given why we believe these results obtained with patients manifesting fully developed PD will apply as well to PD patients in preclinical stages-a topic for future study. We also suggest that these findings point to a potential disease altering therapy for PD once the early diagnosis is established.
摘要：
到临床阐明时，大多数PD患者的帕金森病（PD）病理已很好地发展，这一事实证明了早期诊断的重要性。我们实现这一目标的尝试利用了我们先前的发现，即GM1神经节苷脂在包括血细胞在内的散发性PD（sPD）患者的几乎所有组织中均以低于正常水平的表达。GM1存在于大多数脊椎动物细胞中，在神经元中特别丰富，它对它们的有效功能和长期生存能力至关重要。我们已经利用外周血单核细胞（PBMC），尽管GM1较低,但我们发现,与年龄匹配的健康对照组相比,sPD患者的GM1水平显著较低.为了量化GM1（和GD1a），我们使用了高效薄层色谱法结合与辣根过氧化物酶相关的霍乱毒素B，其次是光密度定量。在葡萄糖脑苷脂酶基因(PD-GBA)突变的PD患者的PBMC中,GM1也存在缺陷,显然比SPD还低.给出了为什么我们相信这些表现出完全发展的PD的患者获得的结果也将适用于临床前阶段的PD患者的原因，这是未来研究的主题。我们还建议，一旦建立了早期诊断，这些发现就表明了PD的潜在疾病改变疗法。
