Human 3D Neuro-Vascular Interaction and Meningeal Lymphatic Models with Application to Alzheimer’s Disease
人体 3D 神经血管相互作用和脑膜淋巴模型在阿尔茨海默病中的应用
基本信息
- 批准号:10396570
- 负责人:
- 金额:$ 51.63万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-05-01 至 2026-04-30
- 项目状态:未结题
- 来源:
- 关键词:3-DimensionalAD transgenic miceAbeta clearanceAddressAffectAlzheimer&aposs DiseaseAlzheimer&aposs disease brainAlzheimer&aposs disease modelAlzheimer&aposs disease pathologyAlzheimer&aposs disease patientAmyloid beta-ProteinAntibodiesAstrocytesBiological MarkersBiological ModelsBloodBlood - brain barrier anatomyBlood CellsBlood VesselsBrainBrain ChemistryBrain PathologyCell Culture TechniquesCellsCerebral Amyloid AngiopathyCerebrospinal FluidClinicalComplexDeep Cervical Lymph NodeDementiaDepositionDevelopmentDisease ProgressionDisease modelElderlyEndothelial CellsEnvironmentEventExtracellular MatrixGenetic TranscriptionGoalsHealthcareHumanImmuneImpaired cognitionImpairmentIn VitroIntercellular FluidInterventionLiquid substanceLymphaticLymphatic SystemLymphatic functionLymphocyteMeningeal lymphatic systemMeningesMicrofluidic MicrochipsMicrofluidicsMicrogliaModelingMolecularMonitorNeuraxisNeurodegenerative DisordersNeurofibrillary TanglesNeuronsOrganoidsPathogenicityPathologicPathologyPathway interactionsPeptidesPericytesPersonsPhagocytosisPharmaceutical PreparationsPhysiologicalPopulationProcessPropertyRoleSenile PlaquesStructureSystemTechnologyTestingTherapeutic InterventionUnited Statesage relatedaging populationbrain parenchymacandidate markercell behaviorcell typedesigndisease-in-a-dishdrug discoveryexperiencehuman diseasehyperphosphorylated tauin vitro Modelin vivoinduced pluripotent stem cellinterestinterstitiallymphatic circulationlymphatic dysfunctionlymphatic vesselmicrofluidic technologyneurovascularneurovascular unitnew therapeutic targetstem cellstau Proteinsthree-dimensional modelingtooltranscriptome sequencing
项目摘要
PROJECT SUMMARY
As the elderly population increases, the number of people with Alzheimer's disease (AD) is rising rapidly. There
is, therefore, a growing interest in the development of in vitro human disease models to better understand and
study the physiological and pathological mechanisms associated with AD. Emerging evidence has implicated an
early breakdown of the BBB in AD patients, even before the cognitive decline and brain pathology. In addition,
meningeal lymphatics are responsible for clearance of Aβ peptides from the brain parenchyma, and disruption
of meningeal lymphatics in AD transgenic mice accelerates Aβ deposition in the meninges, aggravates
parenchymal Aβ accumulation, and induces cognitive impairment. Yet, our understanding of the role of fluid
transport across the BBB, through the brain parenchyma, and exiting via the lymphatic system is poorly
understood. Therefore, the development of physiologically realistic human neural cell culture models of AD with
a neurovascular unit and meningeal lymphatic vessels is urgently needed to dissect molecular mechanisms
underlying the pathogenic cascade of AD and accelerate the discovery of new AD drugs. Building on our
extensive set of preliminary and related studies, we propose to develop a three-dimensional (3D) in vitro model
by integrating BBB, meningeal lymphatics, and stem-cell-derived AD cell culture to closely mimic the AD brain
environment. With this model, we aim to identify AD-specific mechanisms underlying pathophysiological changes
in the BBB, meningeal lymphatics, and Aβ clearance. Our 3D AD model will be useful for not only studying the
mechanisms of AD progression but also for drug discovery in a human brain-like environment.
项目总结
项目成果
期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
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{{ truncateString('SE HOON CHOI', 18)}}的其他基金
Exploring irisin as a novel target for Alzheimers Disease
探索鸢尾素作为阿尔茨海默病的新靶点
- 批准号:
10670486 - 财政年份:2022
- 资助金额:
$ 51.63万 - 项目类别:
Human 3D Neuro-Vascular Interaction and Meningeal Lymphatic Models with Application to Alzheimer’s Disease
人体 3D 神经血管相互作用和脑膜淋巴模型在阿尔茨海默病中的应用
- 批准号:
10179538 - 财政年份:2021
- 资助金额:
$ 51.63万 - 项目类别:
Human 3D Neuro-Vascular Interaction and Meningeal Lymphatic Models with Application to Alzheimer’s Disease
人体 3D 神经血管相互作用和脑膜淋巴模型在阿尔茨海默病中的应用
- 批准号:
10615081 - 财政年份:2021
- 资助金额:
$ 51.63万 - 项目类别:
Exploring irisin as a novel target for Alzheimer's Disease
探索鸢尾素作为阿尔茨海默病的新靶点
- 批准号:
9919511 - 财政年份:2019
- 资助金额:
$ 51.63万 - 项目类别:
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- 批准号:
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- 资助金额:
$ 51.63万 - 项目类别:
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