Novel Approaches to Understand the Pathogenesis and Treat Alzheimer's Disease
了解发病机制和治疗阿尔茨海默病的新方法
基本信息
- 批准号:10428579
- 负责人:
- 金额:$ 239.89万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-06-01 至 2025-05-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAdvisory CommitteesAffectAge of OnsetAllelesAlzheimer&aposs DiseaseAlzheimer&aposs disease modelAlzheimer&aposs disease pathologyAlzheimer&aposs disease related dementiaAmyloidAmyloid beta-ProteinAnimal ModelAnimalsApolipoprotein EAreaAutomobile DrivingAwarenessBehaviorBehavior assessmentBehavioralBindingBioinformaticsBiological MarkersBiometryBiostatistical MethodsBlood VesselsCerebral Amyloid AngiopathyClinicalCollaborationsCommunitiesComplexCongressesConsensusCouplingDataData AnalysesDatabasesDepositionDevelopmentDisease ProgressionEducationEnsureExperimental DesignsGenotypeGoalsImageImmunologyImmunotherapyInterdisciplinary StudyLabelLate Onset Alzheimer DiseaseMagnetic Resonance ImagingMethodologyMethodsMitochondriaMolecular ConformationPathogenesisPathologyPeptoidsPharmaceutical ChemistryPlayPositron-Emission TomographyProgress ReportsProtein ConformationProtein IsoformsProteinsProteomeProteomicsRecording of previous eventsResearchResearch PersonnelRodent ModelRoleSafetySamplingSenile PlaquesSynaptic plasticityTechniquesTechnologyTestingTherapeuticTimeTransgenic MiceTransgenic OrganismsUnited States National Institutes of HealthWorkabeta depositionagedamyloid pathologyapolipoprotein E-3apolipoprotein E-4brain parenchymaclinically relevantdata managementdata sharinggenetic risk factorglucose metabolismhuman datahuman tissueimaging biomarkerimmunoregulationinnovationinsightlaser capture microdissectionmeetingsmouse modelneuroimaging markerneuropathologynovelnovel strategiesnovel therapeuticsoperationpower analysisprogramsresponseside effectsmall moleculesynergismtau Proteinstherapeutic developmenttherapeutically effectivetherapy outcometreatment response
项目摘要
OVERALL PROGRAM SUMMARY/ABSTRACT
In this P01 proposal entitled: “Novel Approaches to Understand the Pathogenesis and Treat Alzheimer’s
Disease”, we seek to gain a better understanding of the heterogeneous pathogenesis of AD and how it is
influenced by apolipoprotein (apo) E isotypes. The apoE4 allele is the major genetic risk factor for late-onset
AD and has been strongly associated with increased amyloid plaques deposition in brain parenchyma and
advanced vascular amyloid pathology; as well as, enhanced Aβ oligomerization. ApoE is also involved in
synaptic plasticity, glucose metabolism, mitochondrial function, and vascular integrity. Currently, there is no
consensus on how different apoE genotypes contribute to the pathogenesis of AD. The interrelated studies
proposed in the three projects of this P01 will help elucidate this complex role of apoE in AD. Hence this P01 is
addressing an issue of great significance. We propose an integrated, multidisciplinary research endeavor that
brings together investigators with an extensive history of successful collaboration, who have expertise in
diverse areas including proteomics, bioinformatics, neuropathology, AD mouse models, immunology, µMRI,
µPET, medicinal chemistry and biomarker studies. Across all projects we will apply our innovative proteomic
methods (with the assistance of the proteomics/neuropathology Core B) and use of common AD models and
behavioral assessments (with the assistance of the transgenic/behavioral Core C), along with state-of-the-art
biomarker technology using SIMOA and P01 investigator developed µMRI methodologies, to ensure synergism
across all P01 studies. Scientific rigor of the P01 will be ensure by the Biostatistics and Bioinformatics Core
(Core D). The three projects of this P01 are focused on the differential role apolipoprotein E (apoE) isoforms
play in: 1) AD plaque and vessel amyloid development as assessed by unbiased proteomics across the full
spectrum of AD pathology (Project 1); 2) innovative therapeutic approaches that target the Aβ/apoE interaction
(Project 2); and 3) responses to our novel therapeutic immunomodulation that targets abnormal conformation
(Project 3). Combined our efforts are anticipated to enhance our understanding of the differential effects of
apoE isotypes on AD pathogenesis and accelerate the discovery of effective therapeutic approaches that
address these diverse roles.
总体方案摘要/摘要
在这份题为《了解阿尔茨海默氏症发病机制和治疗阿尔茨海默氏症的新方法》的P01提案中
疾病“,我们试图更好地了解AD的异质性发病机制以及它是如何
受载脂蛋白E亚型的影响。载脂蛋白E4等位基因是晚发性高血压的主要遗传危险因素
AD与脑实质中淀粉样斑块沉积增加密切相关。
晚期血管淀粉样变性;以及增强的Aβ寡聚。APOE还参与了
突触可塑性、葡萄糖代谢、线粒体功能和血管完整性。目前,没有
关于不同的载脂蛋白E基因型如何在AD的发病机制中起作用的共识。相关研究
在本P01的三个项目中提出的将有助于阐明载脂蛋白E在AD中的这一复杂角色。因此,本P01为
解决一个意义重大的问题。我们提出了一种综合的、多学科的研究努力
将具有广泛成功协作历史的调查人员聚集在一起,他们拥有以下方面的专业知识
包括蛋白质组学、生物信息学、神经病理学、AD小鼠模型、免疫学、µMRI、
µPET、药物化学和生物标志物研究。在所有项目中,我们将应用我们的创新蛋白质组学
方法(在蛋白质组学/神经病理学核心B的辅助下)和使用常见的AD模型和
行为评估(在转基因/行为核心C的帮助下),以及最先进的
使用SiMoA和P01 Investigator的BioMarker技术开发了µMRI方法,以确保协同
在所有P01研究中。生物统计和生物信息学核心将确保P01的科学严谨性
(核心D)。本P01的三个项目集中在载脂蛋白E(ApoE)亚型的不同作用上
参与:1)全面无偏蛋白质组学评估的AD斑块和血管淀粉样蛋白的发展
AD病理学谱(项目1);2)针对Aβ/apoE相互作用的创新治疗方法
(项目2);以及3)对我们针对异常构象的新型治疗性免疫调节的反应
(项目3)。我们的共同努力有望加强我们对不同影响的理解
载脂蛋白E亚型对AD发病机制的影响并加速发现有效的治疗方法
应对这些不同的角色。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
THOMAS M WISNIEWSKI其他文献
THOMAS M WISNIEWSKI的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('THOMAS M WISNIEWSKI', 18)}}的其他基金
Novel Approaches to Understand the Pathogenesis and Treat Alzheimer's Disease
了解发病机制和治疗阿尔茨海默病的新方法
- 批准号:
10621825 - 财政年份:2020
- 资助金额:
$ 239.89万 - 项目类别:
Blocking the binding of Aβ and apoE as a novel therapeutic approach for AD
阻断 Aβ 和 apoE 的结合作为 AD 的新型治疗方法
- 批准号:
10428585 - 财政年份:2020
- 资助金额:
$ 239.89万 - 项目类别:
相似海外基金
Toward a Political Theory of Bioethics: Participation, Representation, and Deliberation on Federal Bioethics Advisory Committees
迈向生命伦理学的政治理论:联邦生命伦理学咨询委员会的参与、代表和审议
- 批准号:
0451289 - 财政年份:2005
- 资助金额:
$ 239.89万 - 项目类别:
Standard Grant