NAPS2 Biofluid Core

NAPS2 生物流体核心

• 批准号: 10674046
• 负责人: PAUL T KOTZBAUER
• 金额: $ 48.48万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10674046
• 关键词: Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer’s disease biomarker; American; Amyloid beta-42; Biochemical; Biological Assay; Biological Markers; Catechols; Cerebrospinal Fluid; Clinical; Clinical Management; Clinical Trials; Collaborations; Collection; Data; Database Management Systems; Dementia with Lewy Bodies; Detection; Development; Diagnosis; Disease; Disease Progression; Ensure; Functional disorder; Future; General Population; Genetic; Goals; Grant; Individual; Intervention; Laboratories; Light; Liquid substance; Measurement; Measures; Multiple System Atrophy; Nerve Degeneration; Neurodegenerative Disorders; Office of Administrative Management; Parkinson Disease; Participant; Pathologic; Pathology; Patients; Phenotype; Plasma; Process; Property; Proteins; REM Sleep Behavior Disorder; Reporting; Research Personnel; Risk; Role; Sampling; Site; Standardization; Technology; Testing; Time; Validation; Work; alpha synuclein; biomarker development; biomarker validation; clinical phenotype; data sharing; drug efficacy; exosome; experience; improved; innovation; interest; neurofilament; neuroimaging; neuroprotection; novel; novel marker; novel strategies; pre-clinical; prevent; programs; protein misfolding cyclic amplification; repository; research study; sample collection; sound; statistics; synuclein; synucleinopathy; tau Proteins; tau-1

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.

摘要：NAPS2 生物流体核心 快速眼动睡眠行为障碍 (RBD) 通常是以下疾病的前驱表现： 病理性 α-突触核蛋白 (aSyn) 蛋白积累（突触核蛋白病）。 RBD 占很大比例 患者最终被诊断患有帕金森病 (PD)、路易体痴呆 (DLB) 和 多系统萎缩（MSA），具有不同的疾病进展速度。开发和验证 RBD 生物标志物可以通过提供目标定量指标来提高未来临床试验的效率 参与度和药物疗效。在北美前驱突触核蛋白病 RBD 联盟中， 第 2 阶段 (NAPS2)，生物流体核心的目标是 1) 监督和协调 [与国家 阿尔茨海默病和相关痴呆症集中存储库 (NCRAD)] 的收集、处理、 在 NAPS2 联盟站点连续收集的血浆和脑脊液 (CSF) 样本的储存； 2) 对已建立的神经退行性标记物进行测定； 3）开发和测试有前途的小说 标记。关键的生物流体标志物包括与神经退行性变相关的测定，例如神经丝 血浆和脑脊液中的轻链 (NfL) 和脑脊液中的总 tau 蛋白，以及与病理相关的测量值 脑脊液中的蛋白质积累，包括总 αSyn、寡聚 αSyn [包括新的错误折叠环状蛋白质 扩增 (PMCA) 技术]、Aβ42、Aβ40 和磷酸化 tau (p-tau181)。努力开发和 测试有前景的新型标记物将包括探索脑脊液中的儿茶酚、探索外泌体 血浆中的标记物，以及通过实时震动诱导转化（RT- 奎IC）。生物流体核心将通过生物流体收集和使用的标准化来确保科学严谨性 在具有丰富经验的实验室进行创新、最先进的生物流体测定。核心 将由突触核蛋白病和其他疾病的生物流体发现和验证领域的领导者指导 神经退行性疾病。核心领导者与 NAPS 研究人员就先前的研究进行了合作 RBD 和其他突触核蛋白病的研究及其先前的经验和指导将确保一致性 作为该联盟的一部分，计划生物流体测定的标准化。所有提议的液体生物标志物测定 有初步数据和可靠的科学证据支持其在突触核蛋白病中的价值。这 Core 将与行政、临床、数据库管理和统计 (DMS) 密切合作 核心以及遗传学、PSG 和神经影像核心，提供经过处理的横截面和 该项目选定标记的纵向数据侧重于预测表型转化。核心将 还提供匿名的横截面和纵向数据，以便与外部调查人员共享。