Neurochemistry Laboratory, Clinical Chemistry Department, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit, 1105 AZ Amsterdam, The Netherlands.
Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit, 1105 AZ Amsterdam, The Netherlands.
Biomolecules. 2020 Aug 12;10(8):1177. doi: 10.3390/biom10081177.
Synaptic degeneration is an early phenomenon in Parkinson's disease (PD) pathogenesis. We aimed to investigate whether levels of synaptic proteins contactin-1 and contactin-2 in cerebrospinal fluid (CSF) of PD patients are reduced compared to dementia with Lewy bodies (DLB) patients and controls and to evaluate their relationship with α-synuclein aggregation. Contactin-1 and -2 were measured in CSF from PD patients ( 58), DLB patients ( 72) and age-matched controls ( 90). Contactin concentration differences between diagnostic groups were assessed by general linear models adjusted for age and sex. Contactin immunoreactivity was characterized in postmortem substantia nigra, hippocampus and entorhinal cortex tissue of PD patients ( 4) and controls ( 4), and its relation to α-syn aggregation was evaluated using confocal laser scanning microscopy. Contactin-1 levels were lower in PD patients (42 (36-49) pg/mL) compared to controls (52 (44-58) pg/mL, 0.003) and DLB patients (56 (46-67) pg/mL, 0.001). Contactin-2 levels were similar across all diagnostic groups. Within the PD patient group, contactin-1 correlated with t-α-syn, tTau and pTau ( 0.30-0.50, 0.05), whereas contactin-2 only correlated with t-α-syn ( 0.34, 0.03). Contactin-1 and -2 were observed within nigral and cortical Lewy bodies and clustered within bulgy Lewy neurites in PD brains. A decrease in CSF contactin-1 may reflect synaptic degeneration underlying Lewy body pathology in PD.
突触退化是帕金森病 (PD) 发病机制中的早期现象。我们旨在研究 PD 患者脑脊液 (CSF) 中的突触蛋白神经联络蛋白-1 和神经联络蛋白-2 水平是否低于路易体痴呆 (DLB) 患者和对照组，并评估它们与α-突触核蛋白聚集的关系。测量了 58 名 PD 患者、72 名 DLB 患者和 90 名年龄匹配的对照组的 CSF 中的接触蛋白-1 和-2。通过调整年龄和性别后的一般线性模型评估诊断组之间的接触蛋白浓度差异。在 PD 患者 (4 例) 和对照组 (4 例) 的黑质、海马和内嗅皮质组织中对接触蛋白免疫反应性进行了特征描述，并使用共聚焦激光扫描显微镜评估了其与α-突触核蛋白聚集的关系。与对照组 (52(44-58)pg/mL， 0.003)和 DLB 患者 (56(46-67)pg/mL， 0.001)相比，PD 患者的接触蛋白-1 水平较低 (42(36-49)pg/mL)。接触蛋白-2 水平在所有诊断组中相似。在 PD 患者组中，接触蛋白-1 与 t-α-突触核蛋白、tTau 和 pTau 呈正相关 (0.30-0.50， 0.05)，而接触蛋白-2 仅与 t-α-突触核蛋白呈正相关 (0.34， 0.03)。在 PD 大脑中，观察到接触蛋白-1 和-2 存在于黑质和皮质路易体中，并聚集在路易氏神经突的隆起处。CSF 中接触蛋白-1 的减少可能反映了 PD 路易体病理学中突触退化的基础。
