Department of Digestive Diseases,, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Neurology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Neuropathol Appl Neurobiol. 2019 Jun;45(4):398-409. doi: 10.1111/nan.12524. Epub 2018 Nov 15.
The prognostic significance of misfolded α-synuclein (α-Syn) aggregates in Parkinson's disease (PD) has not been well investigated. The aim of this study was to reveal the relationship between misfolded α-Syn aggregate concentration in cerebrospinal fluid (CSF) and cognitive decline risk in PD.
A total of 278 patients with PD were retrospectively included. They were diagnosed between 2011 and 2013. The end-point was 2016, and the follow-up period was 54.3 ± 10.0 months. Cognitive decline was defined as a 4-point decrease in the Mini-Mental State Examination score during follow-up. Misfolded α-Syn aggregate concentration in baseline CSF was measured using the protein misfolding cyclic amplification (PMCA) technique. Time to reach 50% of the maximum fluorescence value was recorded.
The PMCA technique successfully detected the level of misfolded α-Syn aggregates in CSF with a sensitivity of 85.3% and a specificity of 91.4%. The time to reach 50% of the maximum fluorescence value was shorter in the patients with cognitive decline than in the patients without cognitive decline (190.7 ± 40.1 h vs. 240.8 ± 45.6 h, P < 0.001). Multifactorial Cox regression analysis revealed that reaching 50% of the maximum fluorescence value in ≤219 h at baseline was associated with increased risk of cognitive decline during the follow-up (HR: 4.90, 95% CI: 2.75-8.74, P < 0.001).
Baseline concentration of misfolded α-Syn aggregates in CSF measured by the PMCA technique predicts risk of cognitive decline in PD.
未折叠的α-突触核蛋白（α-Syn）聚集体在帕金森病（PD）中的预后意义尚未得到充分研究。本研究旨在揭示脑脊液（CSF）中未折叠的α-Syn 聚集浓度与 PD 认知下降风险之间的关系。
共纳入 278 例 PD 患者，均为 2011 年至 2013 年间诊断。终点为 2016 年，随访时间为 54.3±10.0 个月。认知下降定义为随访期间 Mini-Mental State Examination 评分下降 4 分。采用蛋白错误折叠循环扩增（PMCA）技术测量基线 CSF 中未折叠的 α-Syn 聚集浓度。记录达到最大荧光值的 50%所需的时间。
PMCA 技术成功检测到 CSF 中未折叠的 α-Syn 聚集物水平，其灵敏度为 85.3%，特异性为 91.4%。达到最大荧光值的 50%所需的时间在认知下降患者中比在无认知下降患者中更短（190.7±40.1 h 比 240.8±45.6 h，P<0.001）。多因素 Cox 回归分析显示，基线时达到最大荧光值的 50%≤219 h 与随访期间认知下降风险增加相关（HR：4.90，95%CI：2.75-8.74，P<0.001）。
PMCA 技术测量的 CSF 中未折叠的 α-Syn 聚集物的基线浓度可预测 PD 认知下降的风险。
