NAPS2 Biofluid Core

NAPS2 生物流体核心

• 批准号: 10457859
• 负责人: PAUL T KOTZBAUER
• 金额: $ 48.95万
• 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 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10457859
• 关键词: Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer’s disease biomarker; American; Amyloid beta-42; Back; 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; experience; improved; innovation; interest; neurofilament; neuroimaging; 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 REM睡眠行为障碍（RBD）通常是由 病理α-核蛋白（ASYN）蛋白积累（突触核酸）。 RBD很大一部分 患者有时被诊断出患有帕金森氏病（PD），有路易尸体的痴呆症（DLB）和 多系统萎缩（MSA），疾病进展率有所不同。发展和验证 RBD的生物标志物可以通过为目标提供定量指标来提高未来临床试验的效率 参与和药物效率。在RBD的北美前驱剧局疾病联盟中， 第2阶段（NAPS2），生物流体核心的目标将为1）监督和协调[与国家 阿尔茨海默氏病和相关痴呆症（NCRAD）的集中存储库]收集，加工， 以及在NAPS2联盟部位的串行收集的血浆和脑脊液（CSF）样品的存储； 2）执行已建立的神经退行性标记的测定； 3）开发和测试有希望的小说 标记。关键的生物流体标记包括与神经丝等神经变性相关的测定法 血浆和CSF中的轻链（NFL）以及CSF中的总tau，以及与病理相关的测量 蛋白质在CSF中的蛋白质积累，包括总αSyn，低聚αSyn[包括新的蛋白质折叠环状 扩增（PMCA）技术]，Aβ42，Aβ40和磷酸化的tau（P-TAU181）。开发和 测试有希望的新颖标记将包括对CSF中的儿茶酚的探索，外泌体的探索 血浆中的标记和通过实时Quakic诱导的转化率（RT- quic）。生物流体核心将通过标准化生物流体收集和使用来确保科学严格 具有丰富先前经验的实验室进行的创新，最先进的生物流体测定法。核心 将由生物流体发现的领导者指导和在突触核生发病和其他方面的验证 神经退行性疾病。核心领导与小睡调查员合作了先前的研究 在RBD和其他突触核心病中进行研究，其先前的经验和指导将确保一致性 作为该财团的一部分，计划的生物流体测定法的标准化。所有建议的流体生物标志物测定 由初步数据和可靠的科学证据支持，这些证据支持其在突触核心病中的价值。 核心将与行政，临床和数据库管理和统计（DMS）紧密合作 核心，以及遗传学，PSG和神经影像核，提供了处理的横截面和 该项目的选定标记的纵向数据重点是预测表现。核心意愿 还提供匿名的横截面和纵向数据，以与外部研究人员共享。