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（由适用提供）：脉络丛（CP）在血液和脑脊液（CSF）之间形成界面，并与脑毛细血管协同合作，以确保整个大脑中的液体稳态。 CP由心室CSF和另一侧界定在另一侧，另一方面是由密集的，高度可渗透的血管网络限制的，其中包含血液CSF屏障，这是一个单层的上皮细胞，这些细胞向大脑中的大多数CSF秘密，并通过tiht tiht层间插条的优点调节了大粒细胞之间的血液中血细胞的交换，从而调节了大脑的交换。一旦穿过障碍物，便士就会将其吸收到静脉血液中或与间质液混合到大脑表面，并将其深入实质。阿尔茨海默氏病（AD）是古老的痴呆症最常见的形式，淀粉样蛋白肽的积累是该疾病的组织病理学标志。 CP中AD的淀粉样蛋白水平增加，可能会改变CP的渗透性。我们假设渗透性障碍可能对CSF流体动力学产生很大的影响，并增加整个大脑的淀粉样蛋白浓度。拟议的项目将使用超高的场动态对比度增强磁共振成像和隔室组织模型，该模型明确说明了班级间的水交换，以量化体内的CP渗透率，并确定与早期AD中认知功能相关的程度。我们预计，CP渗透性的准确性，非侵入性测量以及认知评估将提供对血液-CSF屏障在 角色广告的认知下降。此类信息对于理解AD的病理生理学和初期疾病的合理治疗将很重要。