Small vessel disease biomarkers in a longitudinally-followed "stroke-belt" cohort

纵向跟踪“中风带”队列中的小血管疾病生物标志物

• 批准号: 9768251
• 负责人: GREGORY A JICHA
• 金额: $ 113.53万
• 依托单位: UNIVERSITY OF KENTUCKY
• 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 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9768251
• 关键词: 3-Dimensional; ABCC9 gene; Address; Affect; Alzheimer' s Disease; Alzheimer’s disease biomarker; Amyloid beta-Protein; Angiogenic Proteins; Applications Grants; Basic Science; Biological Markers; Biometry; Brain; Brain Diseases; Brain Pathology; Cerebral small vessel disease; Cerebrovascular Disorders; Cerebrum; Clinical; Clinical Trials; Cognition; Comorbidity; Data; Dementia; Diagnosis; Diffusion; Disease; Disease Progression; Elderly; Ensure; Foundations; Genetic Polymorphism; Genotype; Goals; Image; Impaired cognition; Individual; Inflammatory; Infrastructure; Injury; Interleukin-12; Kentucky; Liquid substance; Longitudinal Studies; Longitudinal cohort; Magnetic Resonance Imaging; Measures; Microvascular Dysfunction; Monitor; Neurofilament-M; Neuropsychology; Participant; Pathology; Patients; Perfusion; Phase; Plasma; Population; Process; Proteins; Public Health; Recording of previous events; Research; Research Personnel; Resource Sharing; Risk; Sampling; Severities; Spatial Distribution; Spin Labels; Stroke Belt; Subcategory; TNF gene; Therapeutic Intervention; Time; Translational Research; United States National Institutes of Health; Universities; Vascular Diseases; White Matter Hyperintensity; Work; accurate diagnosis; biomarker development; candidate marker; cerebrovascular pathology; cohort; data sharing; effective intervention; experience; imaging biomarker; imaging modality; medical specialties; member; multidisciplinary; pre-clinical; predictive marker; prognostic value; recruit; response; success; targeted treatment; tau Proteins; therapeutic development; vascular cognitive impairment and dementia; vascular contributions

Abstract Vascular contributions to cognitive impairment and dementia (VCID) describes cognitive impairment resulting from cerebrovascular disease or dysfunction. VCID is a frequent co-morbidity with Alzheimer's disease (AD), as well as a single dementia-causing entity. The most common vasculopathy associated with cognitive impairment is cerebral small vessel disease (SVD). It is highly likely that SVD significantly contributes to the clinical manifestation of dementia, and therefore is a viable target for disease-modifying therapies, whether alone or in combination with AD-targeting therapies. One major obstacle for therapeutic development is the lack of biomarkers that are predictive of the presence and course of SVD-VCID. In this proposal we present candidate biomarkers for SV-VCID that will contribute to the consortium. We have identified MRI imaging modalities of 3D FLAIR, ASL, and DTI as our imaging candidate biomarkers. We have also identified IL-12 p70, TNFα, PIGF and VEGFD as our candidate fluid biomarkers that discriminate SVD well in the subset of our cohort that we have analyzed. In this application we have a plan for developing our candidate biomarkers and validating them through the UH2 phase an individual research group, and also through the UH3 part as a member of the consortium. In addition, we bring significant strengths that will help synergize and move the consortium as a whole forward in our collective goal of developing biomarkers that are ready for large scale clinical trials and FDA qualification in years 6-7 of the consortium. These strengths include a well characterized, longitudinal cohort supported through our ADC and other NIH initiatives, our long history of active participation in consortia providing the experience and infrastructure needed to ensure success in this UH2/UH3 mechanism, our history of data sharing, resource sharing including samples, recruitment of research participants for longitudinal studies, and our foundation in basic and translational science.

摘要