In vivo permeability of the human blood-cerbrospinal fluid barrier in dementia

痴呆症中人血脑脊液屏障的体内通透性

• 批准号: 9134651
• 负责人: VALERIE C ANDERSON
• 金额: $ 19.25万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-15 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9134651
• 关键词: Abeta clearance; Accounting; Alzheimer' s Disease; Amyloid; Amyloid beta-Protein; Attention; Biological Markers; Blood; Blood Vessels; Brain; Cerebrospinal Fluid; Cerebrum; Cognition; Data; Dementia; Detection; Development; Diagnosis; Disease; Drug Kinetics; Elderly; Epithelial; Epithelial Cells; Epithelium; Equilibrium; Extravasation; Functional disorder; Goals; Health; Homeostasis; Human; Impaired cognition; Intercellular Fluid; Intercellular Junctions; Intraventricular; Investigation; Knowledge; Laboratories; Life; Liquid substance; Magnetic Resonance Imaging; Measurement; Measures; Memory; Metabolism; Microvascular Permeability; Modeling; Molecular; Neurofibrillary Tangles; Neuropsychological Tests; Noise; Pathogenesis; Patients; Permeability; Process; Production; Protons; Reagent; Relaxation; Role; Side; Signal Transduction; Speed; Structure; Structure of choroid plexus; Surface; Symptoms; Testing; Tissue Model; Tissues; Venous; Ventricular; Water; Work; abeta accumulation; aging brain; amyloid peptide; base; blood cerebrospinal fluid barrier; cerebral capillary; cognitive change; cognitive function; cognitive testing; contrast enhanced; curve fitting; design; executive function; imaging biomarker; improved; in vivo; insight; macromolecule; magnetic field; neuroimaging; neuropsychological; neurotransmission; novel therapeutic intervention; peripheral blood; pharmacokinetic model; solute; ventricular system

DESCRIPTION (provided by applicant): The choroid plexus (CP) forms an interface between the blood and cerebrospinal fluid (CSF) and works in concert with brain capillaries to assure fluid homeostasis throughout the brain. Bounded on one side by ventricular CSF and on the other by a dense, highly permeable vascular network, the CP contains the blood- CSF barrier, a single layer of epithelial cells that secrete the majority of CSF in the brain and, by virtue of tiht intercellular junctions, regulates the exchange of macromolecules between the blood and CSF. Once across the barrier, solutes are transported to the surface of the brain where they are absorbed into the venous blood or mix with interstitial fluid and are carried deep into the parenchyma. Alzheimer's disease (AD) is the most commonly diagnosed form of dementia in the elderly and the accumulation of amyloid-� peptides the histopathological hallmark of the disease. Amyloid-� levels in the CP increase in AD and could alter the permeability of the CP. We hypothesize that permeability disturbances could have large effects on CSF hydrodynamics and increase concentrations of amyloid-� throughout the brain. The proposed project will use ultra-high field dynamic contrast enhanced magnetic resonance imaging and a compartmental tissue model that explicitly accounts for intercompartmental water exchange to quantify CP permeability in vivo and determine the extent to which it is associated with cognitive function in early AD. We expect that the accurate, non-invasive measurement of CP permeability, together with cognitive assessments, will provide critical insight into the role of the blood-CSF barrier in the cognitive decline that characterizes AD. Such information will be important in understanding the pathophysiology of AD and the rational treatment of incipient disease.

描述（由申请人提供）：脉络丛（CP）形成血液和脑脊液（CSF）之间的界面，并与脑毛细血管协同工作，以确保整个大脑的液体稳态。CP的一侧由脑室CSF限制，另一侧由致密的高渗透性血管网限制，CP包含血- CSF屏障，即分泌脑中大部分CSF的单层上皮细胞，并通过紧密的细胞间连接调节血液和CSF之间的大分子交换。一旦穿过屏障，溶质被转运到脑表面，在那里它们被吸收到静脉血中或与间质液混合并被深入到脑实质中。阿尔茨海默氏病（AD）是老年人最常见的痴呆症，淀粉样肽的积累是该疾病的组织病理学标志。CP中淀粉样蛋白β水平在AD中增加，并可改变CP的通透性。我们推测，渗透性障碍可能对CSF流体动力学有很大的影响，并增加整个大脑中淀粉样蛋白的浓度。拟议的项目将使用超高场动态对比增强磁共振成像和明确说明房室间水交换的房室组织模型，以量化体内CP渗透性，并确定其与早期AD认知功能相关的程度。我们期望CP渗透性的准确、非侵入性测量，以及认知评估，将提供对血-CSF屏障在以下方面的作用的重要见解： AD的认知能力下降这些信息将是重要的，在了解AD的病理生理和早期疾病的合理治疗。