Department of Pathology, Peking University Health Science Centre and Third Hospital, Beijing 100191, China; Department of Pathology, University of Washington School of Medicine, Seattle, WA 98104-2499, USA.
Department of Pathology, University of Washington School of Medicine, Seattle, WA 98104-2499, USA.
Neurobiol Dis. 2018 Aug;116:53-59. doi: 10.1016/j.nbd.2018.04.015. Epub 2018 Apr 27.
Plasma total and nervous system derived exosomal (NDE) α-synuclein have been determined as potential biomarkers of Parkinson's disease (PD). To explore the utility of plasma α-synuclein in the prodromal phase of PD, plasma total and NDE α-synuclein were evaluated in baseline and 2-year follow-up samples from 256 individuals recruited as part of the Parkinson's Associated Risk Syndrome (PARS) study. The results demonstrated that baseline and longitudinal increases in total α-synuclein predicted progression of cognitive decline in hyposmic individuals with dopamine transporter (DAT) binding reduction. On the other hand, a longitudinal decrease in NDE α-synuclein predicted worsening cognitive scores in hyposmic individuals with DAT binding reduction. Finally, in individuals with faster DAT progression, decreasing NDE/total α-synuclein ratio was associated with a larger reduction in DAT from baseline to follow-up. These results suggest that, though underlying mechanisms remain to be defined, alterations in plasma total and NDE α-synuclein concentrations are likely associated with PD progression, especially in the aspect of cognitive impairment, at early stages of the disease.
血浆总蛋白和神经系统衍生的外泌体 (NDE) α-突触核蛋白已被确定为帕金森病 (PD) 的潜在生物标志物。为了探索血浆 α-突触核蛋白在 PD 前驱期的效用，我们评估了作为帕金森相关风险综合征 (PARS) 研究一部分招募的 256 名个体的基线和 2 年随访样本中的血浆总蛋白和 NDE α-突触核蛋白。结果表明，基线和总 α-突触核蛋白的纵向增加预测了具有多巴胺转运体 (DAT) 结合减少的嗅觉障碍个体认知能力下降的进展。另一方面，NDE α-突触核蛋白的纵向减少预测了具有 DAT 结合减少的嗅觉障碍个体认知评分的恶化。最后，在 DAT 进展较快的个体中，NDE/总 α-突触核蛋白比值的降低与从基线到随访时 DAT 的减少更大相关。这些结果表明，尽管潜在机制仍有待确定，但血浆总蛋白和 NDE α-突触核蛋白浓度的改变可能与 PD 的进展有关，尤其是在疾病的早期阶段认知障碍方面。
