α-突触核蛋白作为路易体痴呆症潜在的脑脊液生物标志物。

α-Synuclein species as potential cerebrospinal fluid biomarkers for dementia with lewy bodies.

机构信息

Department of Neurology and Alzheimer Center, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands.

Neurological Disorders Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha, Qatar.

出版信息

Mov Disord. 2018 Nov;33(11):1724-1733. doi: 10.1002/mds.111. Epub 2018 Nov 15.

DOI:10.1002/mds.111

PMID:30440090

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6519232/

Abstract

BACKGROUND

The objective of this study was to investigate the discriminating value of a range of CSF α-synuclein species for dementia with Lewy bodies compared with Alzheimer's disease, PD, and cognitively normal controls.

METHODS

We applied our recently published enzyme-linked immunosorbent assays to measure the CSF levels of total α-synuclein, oligomeric α-synuclein, and phosphorylated α-synuclein in dementia with Lewy bodies (n = 42), Alzheimer's disease (n = 39), PD (n = 46), and controls (n = 78). General linear models corrected for age and sex were performed to assess differences in α-synuclein levels between groups. We used backward-elimination logistic regression analysis to investigate the combined discriminating value of the different CSF α-synuclein species and Alzheimer's disease biomarkers.

RESULTS

CSF levels of total α-synuclein were lower in dementia with Lewy bodies and PD compared with Alzheimer's disease as well as controls (P < 0.001). In contrast, CSF levels of oligomeric α-synuclein were higher in dementia with Lewy bodies and PD compared with Alzheimer's disease (P < 0.05) and controls (P < 0.001). No group differences were found for phosphorylated α-synuclein. In dementia with Lewy bodies and PD, CSF total α-synuclein levels positively correlated with tau and phosphorylated tau (both r > 0.40, P < 0.01), but not with amyloid-β . The optimal combination to differentiate dementia with Lewy bodies from controls consisted of amyloid-β , tau, total α-synuclein, oligomeric α-synuclein, age, and sex (AUC, 0.90). To differentiate dementia with Lewy bodies from Alzheimer's disease, the combination of tau and oligomeric α-synuclein resulted in an AUC of 0.83. CSF α-synuclein species do not contribute to the differentiation of dementia with Lewy bodies from PD.

CONCLUSIONS

CSF α-synuclein species could be useful as part of a biomarker panel for dementia with Lewy bodies. Evaluating both oligomeric α-synuclein and total α-synuclein in CSF helps in the diagnosis of dementia with Lewy bodies. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

摘要

背景

本研究旨在探讨一系列 CSF α-突触核蛋白种类对路易体痴呆与阿尔茨海默病、帕金森病和认知正常对照的鉴别价值。

方法

我们应用最近发表的酶联免疫吸附测定法测量路易体痴呆（n=42）、阿尔茨海默病（n=39）、帕金森病（n=46）和对照组（n=78）的 CSF 总α-突触核蛋白、寡聚体α-突触核蛋白和磷酸化α-突触核蛋白水平。为了评估组间 α-突触核蛋白水平的差异，我们进行了校正年龄和性别的一般线性模型。我们使用向后消除逻辑回归分析来研究不同 CSF α-突触核蛋白种类和阿尔茨海默病生物标志物的联合鉴别价值。

结果

与阿尔茨海默病和对照组相比，路易体痴呆和帕金森病的 CSF 总α-突触核蛋白水平较低（P<0.001）。相反，路易体痴呆和帕金森病的 CSF 寡聚体α-突触核蛋白水平高于阿尔茨海默病（P<0.05）和对照组（P<0.001）。未发现磷酸化α-突触核蛋白的组间差异。在路易体痴呆和帕金森病中，CSF 总α-突触核蛋白水平与 tau 和磷酸化 tau 呈正相关（均 r>0.40，P<0.01），但与淀粉样蛋白-β无关。将淀粉样蛋白-β、tau、总α-突触核蛋白、寡聚体α-突触核蛋白、年龄和性别相结合，是区分路易体痴呆与对照组的最佳组合（AUC，0.90）。为了将路易体痴呆与阿尔茨海默病区分开来，tau 和寡聚体α-突触核蛋白的组合产生的 AUC 为 0.83。CSF α-突触核蛋白种类对路易体痴呆与帕金森病的鉴别无贡献。