Validation of Biomarkers of Small Vessel Injury in VCID

VCID 中小血管损伤生物标志物的验证

• 批准号: 10369502
• 负责人: Gary Allen Rosenberg
• 金额: $ 244.17万
• 依托单位: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-30 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10369502
• 关键词: Advisory Committees; Alzheimer' s Disease; Biological; Biological Assay; Biological Markers; Blood; Blood specimen; Cerebral Amyloid Angiopathy; Cerebral small vessel disease; Cerebrospinal Fluid; Classification; Clinical; Clinical Trials; Cognitive; Collaborations; Collection; Data; Dementia; Development; Diffuse; Diffusion Magnetic Resonance Imaging; Disease; Endothelium; Functional disorder; Future; Goals; Grant; Growth; Image; Inflammation; Inflammatory; Injury; Lead; Lesion; Light; Liquid substance; Longitudinal Studies; Magnetic Resonance Imaging; Measurement; Measures; Microvascular Dysfunction; Neuropsychological Tests; Neuropsychology; New Mexico; PGF gene; Participant; Patient Recruitments; Patients; Play; Population; Preparation; Research; Research Subjects; Role; Running; Sampling; Series; Signal Transduction; Site; Skeleton; Surrogate Markers; Test Result; Testing; Time; United States National Institutes of Health; Universities; Validation; Vascular Cognitive Impairment; Vascular Diseases; Water; White Matter Hyperintensity; Work; biomarker evaluation; biomarker validation; cerebrovascular; clinical examination; cognitive performance; cognitive testing; cohort; exosome; imaging biomarker; imaging study; instrument; large datasets; machine learning method; magnetic resonance imaging biomarker; mixed dementia; neurofilament; neuroimaging; neuroimaging marker; potential biomarker; recruit; response; single molecule; vascular cognitive impairment and dementia; white matter

This proposal is in response to RFA-NS-21-005, which is a continuation of RFA-NS-16-020. The overall goal of the project is to study the impact of vascular disease on Alzheimer’s disease (AD). Small vessel disease is the major vascular disease associated with dementia. Cerebral small vessel diseases such as arteriolosclerosis and cerebral amyloid angiopathy are independently associated with worse cognitive performance and greater likelihood of vascular cognitive impairment and dementia (VCID). MarkVCID1 consortium shared subject clinical neuropsychological test data, MRI results and biological samples to validate the biomarkers. The NIH identified 11 biomarkers from MarkVCID1 that could be used in future clinical trials. The UNM site made major contributions to both the MRI and fluid biomarkers: UNM and UCD led the work on the Free Water (FW) biomarker, and contributed data to all of the other MRI biomarkers. UNM was one of the few centers that collected cerebrospinal fluid (CSF) and matched blood on all subjects, contributing to all of the fluid biomarkers selected to move into MarkVCID2. Our group contributed CSF and blood samples to multiple sites for validation of the angiogenic and inflammatory biomarker kits, including CSF placental growth factor (PlGF), and blood exosomes and endothelial inflammation kits. We used MesoScale Discovery assays for fluid analysis, and have recently purchased a Quanterix HD-X single molecule assay (SIMOA) instrument that we will use it to measure neurofilament light (NfL) and PlGF. The UNM Specific aims are: 1) to continue to lead to development of the FW biomarker kit in collaboration with UCD to make this trial ready and to add imaging data to the other MRI biomarkers kits; 2) to continue to collect CSF and blood samples to contribute to the validation of all the CSF and blood biomarker kits; and 3) to recruit 200 new underrepresented patients over two years to add to legacy subjects. UMN anticipates to have longitudinal data for 3 years on many participants. UNM has a large number of patients with VCID, AD, and mixed dementias, as well as subjective cognitive complaints that have been studied as part of two RO1 grants (2006-2016) and the MarkVCID1 (2016- present) with data on clinical cognitive test results, MRI, CSF, and blood. Many of these patients have longitudinal data from multiple follow-ups. UNM is committed to achieving the goals and milestones laid out by NIH for MarkVCID2, and to contribute to the completion of the evaluation of the biomarkers that will be used with study-ready cohorts for clinical trials in vascular cognitive impairment.

该提案是对RFA-NS-21-005的回应，后者是RFA-NS-16-020的延续。该项目的总体目标是研究血管疾病对阿尔茨海默氏病（AD）的影响。小血管疾病是与痴呆有关的主要血管疾病。脑小血管疾病，例如小动脉粥样硬化和脑淀粉样血管病，与认知性能较差，血管认知障碍和痴呆（VCID）独立相关。 MarkVCID1财团共享主题临床神经心理测试数据，MRI结果和生物标志物，以验证生物标志物。 NIH确定了MarkVCID1的11种生物标志物，可以在以后的临床试验中使用。 UNM站点对MRI和流体生物标志物做出了重大贡献：UNM和UCD领导了自由水（FW）生物标志物的工作，并向所有其他MRI生物标志物贡献了数据。 UNM是收集脑脊液（CSF）并在所有受试者上匹配血液的少数几个中心之一，这有助于所有被选为MarkVCID2的流体生物标志物。我们的小组为多个地点贡献了CSF和血液样本，以验证包括CSF占地生长因子（PLGF），以及血液外Nes粒和内皮注射套件在内的血管生成和炎症生物标志物试剂盒。我们使用中尺度的发现分析进行流体分析，并最近购买了Quanterix HD-X单分子测定法（SIMOA）仪器，我们将使用它来测量神经丝（NFL）和PLGF。特定的目的是：1）继续与UCD合作，继续导致FW生物标志物套件的开发，以准备该试验并将成像数据添加到其他MRI生物标志物套件中； 2）继续收集CSF和血液样本，以促进所有CSF和血液生物标志物套件的验证； 3）在两年内招募200名新代表性不足的患者，以增加遗产。 UMN预计将对许多参与者拥有3年的纵向数据。 UNM具有大量患有VCID，AD和混合痴呆症的患者，以及已研究为两种RO1 Grant（2006-2016）的一部分的主观认知抱怨和MarkVCID1（2016-培训）（2016年），以及有关临床认知测试结果的数据，MRI，CSF和血液。这些患者中的许多患者都有来自多个随访的纵向数据。 UNM致力于实现NIH为MarkVCID2提出的目标和里程碑，并为完成生物标志物的评估做出贡献，这些评估将与研究就绪的同伙一起用于血管认知障碍的临床试验。