NAPS2 Biofluid Core
NAPS2 生物流体核心
基本信息
- 批准号:10187085
- 负责人:
- 金额:$ 47.73万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 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:
- 关键词:Alzheimer&aposs DiseaseAlzheimer&aposs disease related dementiaAlzheimer’s disease biomarkerAmericanAmyloid beta-42BackBiochemicalBiological AssayBiological MarkersCatecholsCerebrospinal FluidClinicalClinical ManagementClinical TrialsCollaborationsCollectionDataDatabase Management SystemsDementia with Lewy BodiesDetectionDevelopmentDiagnosisDiseaseDisease ProgressionEnsureFunctional disorderFutureGeneral PopulationGeneticGoalsGrantIndividualInterventionLaboratoriesLightLiquid substanceMeasurementMeasuresMultiple System AtrophyNerve DegenerationNeurodegenerative DisordersOffice of Administrative ManagementParkinson DiseaseParticipantPathologicPathologyPatientsPhenotypePlasmaProcessPropertyProteinsREM Sleep Behavior DisorderReportingResearch PersonnelRiskRoleSamplingSiteStandardizationTechnologyTestingTimeValidationWorkalpha synucleinbiomarker developmentbiomarker validationclinical phenotypedata sharingdrug efficacyexperienceimprovedinnovationinterestneurofilamentneuroimagingnovelnovel markernovel strategiespre-clinicalpreventprogramsprotein misfolding cyclic amplificationrepositoryresearch studysample collectionsoundstatisticssynucleinsynucleinopathytau Proteinstau-1
项目摘要
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:NAPS 2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表现:
病理性α-突触核蛋白(aSyn)蛋白积聚(突触核蛋白病)。大部分RBD
患者最终被诊断患有帕金森病(PD)、路易体痴呆(DLB),以及
多系统萎缩(MSA),具有不同的疾病进展率。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。
参与度和药物功效。在北美RBD前驱突触核蛋白病联盟中,
第二阶段(NAPS 2),生物流体核心的目标将是1)监督和协调[沿着国家
阿尔茨海默氏病和相关痴呆症的集中储存库(NCRAD)]收集,处理,
以及在NAPS 2联合体研究中心储存连续采集的血浆和脑脊液(CSF)样本;
2)进行已建立的神经退行性标志物的测定;和3)开发和测试有前途的新的
标记。关键的生物流体标记物包括与神经变性相关的测定,如神经丝
血浆和CSF中的轻链(NfL)和CSF中的总tau,以及与病理学相关的测量。
CSF中的蛋白质蓄积,包括总αSyn、寡聚αSyn [包括新的蛋白质错误折叠环
扩增(PMCA)技术]、Aβ42、Aβ40和磷酸化tau(p-tau 181)。努力发展和
测试有希望的新标记物将包括探索CSF中的儿茶酚,探索外泌体,
血浆中的标志物,并通过实时振荡诱导转换(RT-10)测量CSF中的αSyn寡聚体。
QuIC)。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的严谨性。
在具有丰富经验的实验室进行创新的、最先进的生物流体分析。核心
将由突触核蛋白病和其他生物流体发现和验证的领导者指导
神经退行性疾病核心领导人与NAPS调查人员合作进行了先前的研究
RBD和其他突触核蛋白病的研究,以及他们之前的经验和指导将确保一致性
以及作为该联盟的一部分的计划生物流体测定的标准化。所有拟定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。的
核心将与行政、临床和数据库管理和统计(DMS)部门密切合作
核心,以及沿着遗传学,PSG和神经影像核心,提供处理过的横截面和
该项目所选标记的纵向数据集中于预测表型转化。芯会
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。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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PAUL T KOTZBAUER其他文献
PAUL T KOTZBAUER的其他文献
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{{ truncateString('PAUL T KOTZBAUER', 18)}}的其他基金
Imaging Ligands for Alpha-Synuclein Fibril Accumulation in Multiple System Atrophy
多系统萎缩中α-突触核蛋白原纤维积累的成像配体
- 批准号:
10452228 - 财政年份:2022
- 资助金额:
$ 47.73万 - 项目类别:
Imaging Ligands for Alpha-Synuclein Fibril Accumulation in Multiple System Atrophy
多系统萎缩中α-突触核蛋白原纤维积累的成像配体
- 批准号:
10581664 - 财政年份:2022
- 资助金额:
$ 47.73万 - 项目类别:
IDENTIFICATION OF FLUORESCENT LIGANDS FOR ALPHA SYNUCLEIN FIBRILS
α 突触核蛋白原纤维荧光配体的鉴定
- 批准号:
9789973 - 财政年份:2018
- 资助金额:
$ 47.73万 - 项目类别:
STRUCTURAL BIOLOGY OF ALPHA-SYNUCLEIN IN LEWY BODY DEMENTIA
路易体痴呆中α-突触核蛋白的结构生物学
- 批准号:
10246509 - 财政年份:2018
- 资助金额:
$ 47.73万 - 项目类别:
STRUCTURAL BIOLOGY OF ALPHA-SYNUCLEIN IN LEWY BODY DEMENTIA
路易体痴呆中α-突触核蛋白的结构生物学
- 批准号:
10473717 - 财政年份:2018
- 资助金额:
$ 47.73万 - 项目类别:
Structural Biology of Alpha-Synuclein in Lewy Body Dementia
路易体痴呆中α-突触核蛋白的结构生物学
- 批准号:
10729722 - 财政年份:2018
- 资助金额:
$ 47.73万 - 项目类别:
STRUCTURAL BIOLOGY OF ALPHA-SYNUCLEIN IN LEWY BODY DEMENTIA
路易体痴呆中α-突触核蛋白的结构生物学
- 批准号:
10023948 - 财政年份:2018
- 资助金额:
$ 47.73万 - 项目类别:
STRUCTURAL BIOLOGY OF ALPHA-SYNUCLEIN IN LEWY BODY DEMENTIA
路易体痴呆中α-突触核蛋白的结构生物学
- 批准号:
9791034 - 财政年份:2018
- 资助金额:
$ 47.73万 - 项目类别:
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