Understanding the contribution of altered cerebrovascular function to the pathology and clinical symptoms of Huntington disease

了解脑血管功能改变对亨廷顿病病理学和临床症状的影响

• 批准号: 10314055
• 负责人: HERMINIA Diana ROSAS
• 金额: $ 66.85万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-12-15 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10314055
• 关键词: Achievement; Activities of Daily Living; Affect; Age; Blood Vessels; Body Weight decreased; Brain; Brain Stem; Cell physiology; Cerebrovascular Circulation; Cerebrovascular Disorders; Cerebrum; Clinical; Cognitive; Core-Binding Factor; Corpus striatum structure; DNA Sequence Alteration; Data; Dependence; Disease; Disease Progression; Equation; Evaluation; Foundations; Functional disorder; Future; Gender; Genes; Genetic; Genetic Transcription; Huntington Disease; Huntington protein; Image; Impaired cognition; Impairment; Individual; Location; Measures; Metabolic dysfunction; Modeling; Motor; Multimodal Imaging; Mutation; Nerve Degeneration; Neurobehavioral Manifestations; Neurodegenerative Disorders; Neurologic; Neurons; Neuropsychological Tests; Organelles; Outcome; Oxidation-Reduction; Parietal; Pathogenesis; Pathology; Pathway interactions; Performance; Perfusion; Pharmaceutical Preparations; Play; Predisposition; Production; Protein Biochemistry; Proteins; Respiration Disorders; Role; Scanning; Severities; Severity of illness; Signal Transduction; Sleep disturbances; Specific qualifier value; Symptoms; System; Testing; Thalamic structure; Thinness; Time; Toxic effect; Visuospatial; arterial spin labeling; brain volume; cerebral atrophy; cerebrovascular; clinical investigation; cognitive performance; cohort; contrast imaging; executive function; imaging approach; interest; motor symptom; multidisciplinary; mutant; neuroimaging; neuroinflammation; neurotropic; neurovascular; novel; psychiatric symptom; putamen; regional atrophy; response; skills; spatiotemporal; synaptic function; white matter

PROJECT SUMMARY/ABSTRACT: This proposal seeks to establish the pathophysiological mechanisms that establish a relationship between neurovascular dysfunction, neurological impairment and brain degeneration in Huntington’s disease (HD). It builds on our growing understanding of the important of neurovascular alterations in neurodegeneration, including in HD, and takes advantage of clinical and neuroimaging expertise as well as the availability of a well-characterized cohort of HD gene-expanded individuals. Aim1 examines the cross- sectional regional changes in cerebrovascular reactivity (CVR) and tests the hypothesis that impaired CVR triggers focal brain atrophy. Aim 2 tests the specific hypothesis that impaired perfusion (CBF) occurs in HD and is associated with regionally altered CVR. Aim 3 evaluates the longitudinal neurovascular changes and the causal relationship between location and severity of these changes with rates of clinical progression and of brain atrophy. Successful achievement of these aims will establish a strong foundation for understanding key vascular mechanisms that may affect progression and HD and establish neurovascular mechanisms as important targets for future clinical drug trials in HD

项目摘要/摘要：本课题旨在建立