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.

本提案是对RFA-NS-21-005的回应，RFA-NS-21-005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病（AD）的影响。小血管疾病是与痴呆相关的主要血管疾病。脑小血管疾病，如小动脉硬化和脑淀粉样血管病与认知能力下降和血管性认知障碍和痴呆（VCID）的可能性增加独立相关。MarkVCID 1联盟分享了受试者的临床神经心理学测试数据、MRI结果和生物样本，以验证生物标志物。NIH从MarkVCID 1中鉴定出11种生物标志物，可用于未来的临床试验。UNM网站对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，并为所有其他MRI生物标志物提供了数据。UNM是少数几个收集所有受试者脑脊液（CSF）和匹配血液的中心之一，有助于选择所有液体生物标志物进入MarkVCID 2。我们的团队向多个研究中心提供CSF和血液样本，用于验证血管生成和炎症生物标志物试剂盒，包括CSF胎盘生长因子（PlGF）以及血液外泌体和内皮炎症试剂盒。我们使用MesoScale Discovery分析进行流体分析，最近购买了Quanterix HD-X单分子分析（SIMOA）仪器，我们将使用它来测量神经丝光（NfL）和PlGF。全国妇女联盟的具体目标是：1）继续与UCD合作开发FW生物标志物试剂盒，使这项试验准备就绪，并将成像数据添加到其他MRI生物标志物试剂盒中; 2）继续收集CSF和血液样本，以促进所有CSF和血液生物标志物试剂盒的验证;和3）在两年内招募200名新的代表性不足的患者，以添加到传统受试者中。UMN预计将有许多参与者的3年纵向数据。UNM有大量VCID，AD和混合性痴呆患者，以及作为两项RO 1赠款（2006-2016）和MarkVCID 1（2016年至今）的一部分研究的主观认知投诉，其中包括临床认知测试结果，MRI，CSF和血液数据。这些患者中的许多人都有来自多次随访的纵向数据。UNM致力于实现NIH为MarkVCID 2制定的目标和里程碑，并为完成将用于血管性认知障碍临床试验的研究就绪队列的生物标志物的评估做出贡献。