Department of Neurology, University Medical Center Goettingen, Göttingen, Germany; and Paracelsus-Elena Klinik, Kassel, Germany.
Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa, USA.
Mov Disord. 2019 Sep;34(9):1354-1364. doi: 10.1002/mds.27806. Epub 2019 Jul 30.
Aggregation of α-synuclein is central to the pathophysiology of PD. Biomarkers related to α-synuclein may be informative for PD diagnosis/progression.
To analyze α-synuclein in CSF in drug-naïve PD, healthy controls, and prodromal PD in the Parkinson's Progression Markers Initiative.
Over up to 36-month follow-up, CSF total α-synuclein and its association with MDS-UPDRS motor scores, cognitive assessments, and dopamine transporter imaging were assessed.
The inception cohort included PD (n = 376; age [mean {standard deviation} years]: 61.7 [9.62]), healthy controls (n = 173; age, 60.9 [11.3]), hyposmics (n = 16; age, 68.3 [6.15]), and idiopathic rapid eye movement sleep behavior disorder (n = 32; age, 69.3 [4.83]). Baseline CSF α-synuclein was lower in manifest and prodromal PD versus healthy controls. Longitudinal α-synuclein decreased significantly in PD at 24 and 36 months, did not change in prodromal PD over 12 months, and trended toward an increase in healthy controls. The decrease in PD was not shown when CSF samples with high hemoglobin concentration were removed from the analysis. CSF α-synuclein changes did not correlate with longitudinal MDS-UPDRS motor scores or dopamine transporter scan.
CSF α-synuclein decreases early in the disease, preceding motor PD. CSF α-synuclein does not correlate with progression and therefore does not reflect ongoing dopaminergic neurodegeneration. Decreased CSF α-synuclein may be an indirect index of changes in the balance between α-synuclein secretion, solubility, or aggregation in the brain, reflecting its overall turnover. Additional biomarkers more directly related to α-synuclein pathophysiology and disease progression and other markers to be identified by, for example, proteomics and metabolomics are needed. © 2019 International Parkinson and Movement Disorder Society.
α-突触核蛋白的聚集是 PD 病理生理学的核心。与 α-突触核蛋白相关的生物标志物可能对 PD 的诊断/进展有帮助。
在帕金森进展标志物倡议中，分析未经药物治疗的 PD、健康对照者和前驱期 PD 中的 CSF 中 α-突触核蛋白。
在长达 36 个月的随访中，评估了 CSF 总 α-突触核蛋白及其与 MDS-UPDRS 运动评分、认知评估和多巴胺转运体成像的相关性。
起始队列包括 PD（n = 376；年龄[平均值{标准差}岁]：61.7 [9.62]）、健康对照者（n = 173；年龄，60.9 [11.3]）、低视力者（n = 16；年龄，68.3 [6.15]）和特发性快速眼动睡眠行为障碍（n = 32；年龄，69.3 [4.83]）。与健康对照组相比，显性和前驱期 PD 的基线 CSF α-突触核蛋白水平较低。PD 在 24 和 36 个月时 CSF α-突触核蛋白显著下降，前驱期 PD 在 12 个月时无变化，健康对照组呈增加趋势。当从分析中去除高血红蛋白浓度的 CSF 样本时，PD 中的 CSF α-突触核蛋白变化未显示出来。CSF α-突触核蛋白的变化与纵向 MDS-UPDRS 运动评分或多巴胺转运体扫描均无相关性。
CSF α-突触核蛋白在疾病早期下降，早于运动 PD。CSF α-突触核蛋白与进展无关，因此不反映持续的多巴胺能神经退行性变。CSF α-突触核蛋白的减少可能是脑内 α-突触核蛋白分泌、可溶性或聚集平衡变化的间接指标，反映了其整体周转率。需要其他更直接与 α-突触核蛋白病理生理学和疾病进展相关的生物标志物以及通过蛋白质组学和代谢组学等方法确定的其他标志物。
Zotero 插件