脑脊髓液中自噬相关蛋白水平可能代表早期帕金森病的潜在新型生物标志物。

Cerebrospinal Fluid Levels of Autophagy-related Proteins Represent Potentially Novel Biomarkers of Early-Stage Parkinson's Disease.

机构信息

Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

Neuroscience Center, Samsung Medical Center, Seoul, Republic of Korea.

出版信息

Sci Rep. 2018 Nov 15;8(1):16866. doi: 10.1038/s41598-018-35376-6.

Abstract

The roles of autophagy-related proteins as diagnostic or monitoring biomarkers in Parkinson's disease (PD) have not been clearly elucidated. We recruited 32 patients with early-stage PD and 28 control subjects, and evaluated parkinsonian motor symptoms and dopamine transporter imaging data. Cerebrospinal fluid (CSF) levels of LC3B, Beclin1, and LAMP-2 were estimated using ELISAs, and CSF levels of ATG5, ATG7, and p62 were examined by immunoblotting. Additionally, we also assessed the levels of α-synuclein, total tau, and phosphorylated tau in CSF using ELISAs. Significant differences in the levels of LC3B, LAMP-2, and Beclin1 were observed between the PD and control groups. Using 29.8 pg/mL as the cut-off value for a diagnostic biomarker of PD, CSF LC3B levels exhibited high sensitivity (96.9%) and specificity (89.3%) with an area under the curve of 0.982. Furthermore, LC3B was significantly correlated with the asymmetry index in the caudate and putamen, as estimated by a semi-quantitative analysis of [F] N-(3-fluoropropyl)-2β-carbon ethoxy-3β-(4-iodophenyl) nortropane (FP-CIT) positron emission tomography (PET). CSF levels of LC3B represented a potential diagnostic and prognostic biomarker of early-stage PD in patients. Based on our findings, molecular biological changes in PD are associated with dysregulation of the lysosomal autophagy pathway.

摘要

自噬相关蛋白在帕金森病(PD)中的诊断或监测生物标志物的作用尚未明确。我们招募了 32 名早期 PD 患者和 28 名对照受试者,并评估了帕金森运动症状和多巴胺转运蛋白成像数据。使用 ELISA 测定 LC3B、Beclin1 和 LAMP-2 的脑脊液(CSF)水平,并通过免疫印迹法检测 ATG5、ATG7 和 p62 的 CSF 水平。此外,我们还使用 ELISA 评估了 CSF 中α-突触核蛋白、总tau 和磷酸化 tau 的水平。PD 组和对照组之间 LC3B、LAMP-2 和 Beclin1 的水平存在显著差异。使用 29.8 pg/mL 作为 PD 诊断生物标志物的截断值,CSF LC3B 水平具有高灵敏度(96.9%)和特异性(89.3%),曲线下面积为 0.982。此外,LC3B 与半定量分析 [F] N-(3-氟丙基)-2β-碳乙氧基-3β-(4-碘苯基)-去甲托烷(FP-CIT)正电子发射断层扫描(PET)估计的尾状核和壳核的不对称指数显著相关。CSF LC3B 水平代表早期 PD 患者潜在的诊断和预后生物标志物。基于我们的发现,PD 中的分子生物学变化与溶酶体自噬途径的失调有关。

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