Feasibility and Safety of Multicenter Tissue and Biofluid Sampling for α-Synuclein in Parkinson's Disease: The Systemic Synuclein Sampling Study (S4)
Feasibility and Safety of Multicenter Tissue and Biofluid Sampling for α-Synuclein in Parkinson's Disease: The Systemic Synuclein Sampling Study (S4)
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DOI：
10.3233/jpd-181434
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发表时间：
2018-01-01
影响因子：
5.2
通讯作者：
Mollenhauer, Brit
中科院分区：
文献类型：
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作者：
Chahine, Lana M.;Beach, Thomas G.;Mollenhauer, Brit
背景：α -突触核蛋白是帕金森病（PD）的主要生物标志物。关于α -突触核蛋白在不同组织和生物体液中作为PD生物标志物的准确性，有相互矛盾的报道，α -突触核蛋白在受试者体内的解剖分布也没有得到很好的描述。系统突触核蛋白取样研究（S4）旨在解决这些知识空白。S4是一项多中心、横断面、观察性研究，评估帕金森氏症和健康对照组（HC）多种组织和生物体液中的α -突触核蛋白。目的：描述S4队列的基线特征以及本研究的安全性和可行性。方法：参与者接受了运动和非运动临床评估、多巴胺转运体SPECT、生物体液采集（脑脊液、唾液和血液）和组织活检（皮肤、乙状结肠和下颌腺）。活检的充分性是根据是否存在足够的靶组织来确定的。用抗未修饰α -突触核蛋白的5C12单克隆抗体对组织切片进行染色。所有标本均以标准化方式采集和处理。系统记录不良事件。结果：最终队列包括82名参与者（61名PD， 21名HC）。68名受试者（83%）获得了所有类型的标本，但只有50名受试者（61%）收集了所有标本并可对α -突触核蛋白进行评估。轻微的不良事件是常见的，特别是在颌下腺活检，但只有1个严重的不良事件发生。结论：α -突触核蛋白的多中心组织和生物液取样是可行的，总体上是安全的。S4将有助于了解PD患者体液和周围神经系统中α -突触核蛋白病理和生物标志物的同时分布。
Background: alpha-synuclein is a lead Parkinson's disease (PD) biomarker. There are conflicting reports regarding accuracy of alpha-synuclein in different tissues and biofluids as a PD biomarker, and the within-subject anatomical distribution of alpha-synuclein is not well described. The Systemic Synuclein Sampling Study (S4) aims to address these gaps in knowledge. The S4 is a multicenter, cross-sectional, observational study evaluating alpha-synuclein in multiple tissues and biofluids in PD and healthy controls (HC).Objective: To describe the baseline characteristics of the S4 cohort and safety and feasibility of this study.Methods: Participants underwent motor and non-motor clinical assessments, dopamine transporter SPECT, biofluid collection (cerebrospinal fluid, saliva, and blood), and tissue biopsies (skin, sigmoid colon, and submandibular gland). Biopsy adequacy was determined based on presence of adequate target tissue. Tissue sections were stained with the 5C12 monoclonal antibody against unmodified alpha-synuclein. All specimens were acquired and processed in a standardized manner. Adverse events were systematically recorded.Results: The final cohort consists of 82 participants (61 PD, 21 HC). In 68 subjects (83%), all types of specimens were obtained but only 50 (61%) of subjects had all specimens both collected and evaluable for alpha-synuclein. Mild adverse events were common, especially for submandibular gland biopsy, but only 1 severe adverse event occurred.Conclusion: Multicenter tissue and biofluid sampling for alpha-synuclein is feasible and generally safe. S4 will inform understanding of the concurrent distribution of alpha-synuclein pathology and biomarkers in biofluids and peripheral nervous system in PD.