NAPS2 Biofluid Core

摘要：NAPS2生物流体芯 REM睡眠行为障碍(RBD)通常是由以下定义的疾病的前驱症状 病理性α-突触核蛋白(ASyn)蛋白积聚(突触核病)。RBD的很大比例 患者最终被诊断为帕金森氏病(PD)，路易体痴呆(DLB)，以及 多系统萎缩(MSA)，疾病进展速度不一。开发和验证 RBD的生物标志物可以通过为靶点提供定量指标来提高未来临床试验的效率 参与度和药物疗效。在关于RBD的北美前驱综合征核病联盟中， 第二阶段(NAPS2)，生物流体核心的目标将是1)监督和协调[与国家 阿尔茨海默病和相关痴呆的中央资料库(NCRAD)]收集、处理、 以及在NAPS2联合体地点储存连续收集的血浆和脑脊液样本； 2)对已建立的神经退行性标志物进行分析；3)开发和测试有前途的新技术 记号笔。关键的生物流体标记物包括与神经退行性变相关的分析，如神经丝 血浆和脑脊液中的轻链(NFL)和脑脊液中的总tau，以及与病理相关的措施 脑脊液中蛋白质的积累包括总α同步蛋白、寡聚α同步蛋白[包括新的蛋白质错折叠环状 扩增技术]、Aβ42、Aβ40和磷酸化tau(p-tau181)。努力发展和发展 测试有前景的新标记物将包括探索脑脊液中的儿茶酚，探索外切体 血浆标志物和脑脊液中α-Syn寡聚体的实时震颤诱导转换(RT-RT)检测 Quic)。生物流体核心将通过标准化生物流体收集和使用确保科学严格性 创新的、最先进的生物流体分析是在拥有丰富经验的实验室进行的。《核心》 将由联体核病和其他生物流体发现和验证领域的领导者指导 神经退行性疾病。核心领导与国家行动方案调查人员就先前的研究进行了合作 对RBD和其他联体核病的研究及其先前的经验和指导将确保一致性 并作为该联盟的一部分，对计划中的生物流体检测进行标准化。所有建议的流体生物标志物分析 有初步数据和可靠的科学证据支持它们在联体核病中的价值。这个 CORE将与行政、临床和数据库管理和统计(DMS)密切合作 与Genetics、PSG和神经成像核心一起，提供经过处理的横断面和 该项目选定的标记的纵向数据侧重于预测表观转化。核心意志 还提供匿名的横断面和纵向数据，以便与外部调查人员共享。

ABSTRACT: NAPS2 BIOFLUID CORE REM sleep behavior disorder (RBD) is commonly a prodromal manifestation of diseases defined by pathologic alpha-synuclein (aSyn) protein accumulation (synucleinopathies). A large percentage of RBD patients are eventually diagnosed with Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), with varying rates of disease progression. Development and validation of biomarkers for RBD can improve the efficiency of future clinical trials by providing quantitative metrics for target engagement and drug efficacy. In the North American Prodromal Synucleinopathy Consortium on RBD, Stage 2 (NAPS2), the aims of the Biofluid Core will be 1) to oversee and coordinate [along with the National Centralized Repository for Alzheimer’s Disease and Related Dementias (NCRAD)] the collection, processing, and storage of serially collected plasma and cerebrospinal fluid (CSF) samples at the NAPS2 consortium Sites; 2) to perform assays of established neurodegenerative markers; and 3) to develop and test promising novel markers. The key biofluid markers include assays that correlate with neurodegeneration such as neurofilament light chain (NfL) in plasma and CSF and total tau in CSF, as well as measures that correlate with pathologic protein accumulation in CSF including total αSyn, oligomeric αSyn [including new protein misfolding cyclic amplification (PMCA) technology], Aβ42, Aβ40, and phosphorylated tau (p-tau181). Efforts on developing and testing promising novel markers will include exploration of catechols in the CSF, exploration of exosomal markers in plasma, and measurement of αSyn oligomers in CSF by real-time quaking-induced conversion (RT- QuIC). The Biofluid Core will ensure scientific rigor through standardization of biofluid collection and use of innovative, state-of-the-art biofluid assays performed at laboratories with extensive prior experience. The Core will be directed by leaders in biofluid discovery and validation in synucleinopathies and other neurodegenerative diseases. The Core leads have collaborated with NAPS investigators on prior research studies in RBD and other synucleinopathies, and their prior experience and guidance will ensure consistency and standardization of planned biofluid assays as part of this consortium. All proposed fluid biomarker assays are backed by preliminary data and sound scientific evidence supporting their value in synucleinopathies. The Core will work closely with the Administrative, Clinical, and Database Management and Statistics (DMS) Cores, and along with the Genetics, PSG and Neuroimaging Cores, supply processed cross-sectional and longitudinal data of selected markers for the Project focused on predicting phenoconversion. The Core will also provide anonymized cross-sectional and longitudinal data for sharing with outside investigators.