Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.
Civin Laboratory for Neuropathology, Banner Sun Health Research Institute, Sun City, AZ, USA.
J Parkinsons Dis. 2018;8(4):517-527. doi: 10.3233/JPD-181434.
α-synuclein is a lead Parkinson's disease (PD) biomarker. There are conflicting reports regarding accuracy of α-synuclein in different tissues and biofluids as a PD biomarker, and the within-subject anatomical distribution of α-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 α-synuclein in multiple tissues and biofluids in PD and healthy controls (HC).
To describe the baseline characteristics of the S4 cohort and safety and feasibility of this study.
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 α-synuclein. All specimens were acquired and processed in a standardized manner. Adverse events were systematically recorded.
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 α-synuclein. Mild adverse events were common, especially for submandibular gland biopsy, but only 1 severe adverse event occurred.
Multicenter tissue and biofluid sampling for α-synuclein is feasible and generally safe. S4 will inform understanding of the concurrent distribution of α-synuclein pathology and biomarkers in biofluids and peripheral nervous system in PD.
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存在相互矛盾的报告，并且α-突触核蛋白在体内的解剖分布尚未得到很好的描述。系统性突触核蛋白采样研究（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 PD 和健康对照组（HC）中多种组织和生物体液中的α-突触核蛋白。
描述 S4 队列的基线特征以及该研究的安全性和可行性。
参与者接受了运动和非运动临床评估、多巴胺转运蛋白 SPECT、生物流体采集（脑脊液、唾液和血液）以及组织活检（皮肤、乙状结肠和颌下腺）。根据是否存在足够的目标组织来确定活检是否充分。使用针对未修饰的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。
最终队列包括 82 名参与者（61 名 PD，21 名 HC）。在 68 名受试者（83%）中，所有类型的标本均获得，但只有 50 名受试者（61%）的所有标本均采集并可评估α-突触核蛋白。轻度不良事件很常见，尤其是颌下腺活检，但仅发生 1 例严重不良事件。
多中心组织和生物体液α-突触核蛋白采样是可行且通常安全的。S4 将为了解 PD 中生物体液和周围神经系统中α-突触核蛋白病理学和生物标志物的并发分布提供信息。
