Core B: Clinical Research Core

项目总结：临床研究核心 帕金森病（PD）是第二常见的神经退行性疾病。虽然目前的治疗方法 缓解与PD相关的症状和残疾，没有治疗减缓或逆转神经退行性疾病， 过程最近的工作指出炎症在PD发病机制中的重要作用。在工作中， P20探索性项目（NS 09530），我们在PD动物模型中发现了先天免疫激活的证据， 并获得了暗示人类样品中免疫调节的初步数据。将这项研究扩展到 更完整地研究PD患者的炎症变化对于确定 在人类疾病的炎症，从而有助于发展潜在的免疫调节性疾病 改良疗法临床研究核心的主要目标是建立一个特征良好的队列 早期特发性PD受试者的神经炎症纵向研究。该队列将 提供临床数据、生物标本和成像数据，直接支持这三个研究项目 在P50补助金下提出。核心将招募、临床评估和每年随访60名年龄和性别- 匹配的对照组和60例UAB时患有早期、未经治疗的特发性PD的受试者。CSF、血浆和外周血 将在基线时采集血液单核细胞（PBMC），并在基线时采集血浆和PBMC。 每年的后续访问。将在基线时对该队列进行[18F]DPA-714 PET成像，以评估中心 早期炎症，特发性PD。所有受试者数据将提交给数据管理部门 NINDS帕金森病生物标志物项目（PDBP）下的资源（DMR），并获得批准 生物样本将被发送到NINDS存储库BioSEND。与哥伦比亚大学合作， 还将招募患有PD（n=20）和未患有PD（n = 20）的LRRK 2 G2019 S携带者，以及LRRK 2 G2019 S非 PD携带者（n=20）和无PD携带者（n=20）。既往患者的生物标本和临床数据 LRRK 2突变的基因分型将直接输入项目3。

PROJECT SUMMARY: CLINICAL RESEARCH CORE Parkinson’s disease (PD) is the second most common neurodegenerative disorder. While current treatments mitigate the symptoms and disability associated with PD, no treatments slow or reverse the neurodegenerative process. Recent work points to a significant role for inflammation in PD pathogenesis. In work supported by the P20 Exploratory Project (NS09530), we found evidence for activation of innate immunity in animal models of PD, and obtained preliminary data implicating immunomodulation in human samples. Expanding this research to a more complete study of inflammatory changes in human subjects with PD is essential to define the role of inflammation in human disease and thus aid in the development of potential immunomodulatory disease modifying therapies. The primary goal of the Clinical Research Core is to establish a well-characterized cohort of early stage, idiopathic PD subjects for longitudinal study with regard to neuroinflammation. This cohort will provide clinical data, biospecimens, and imaging data that will directly support the three research projects proposed under the P50 grant. The Core will recruit, clinically assess, and follow annually 60 age- and sex- matched controls and 60 subjects with early stage, untreated, idiopathic PD at UAB. CSF, plasma, and peripheral blood mononuclear cells (PBMCs) will be collected at baseline, and plasma and PBMCs will be collected at annual follow-up visits. [18F]DPA-714 PET imaging will be performed on this cohort at baseline to assess central inflammation in early stage, idiopathic PD. All participant data will be submitted to the Data Management Resource (DMR) under the NINDS’ Parkinson’s disease Biomarker Program (PDBP), and approved biospecimens will be sent to the NINDS repository BioSEND. In conjunction with Columbia University, the Core will also recruit LRRK2 G2019S carriers with PD (n=20) and without PD (n=20), and LRRK2 G2019S NON- carriers with PD (n=20) and without PD (n=20). Biospecimens and clinical data from patients previously genotyped for mutations in LRRK2 will feed directly into Project 3.