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.
总体计划摘要/摘要
在这份题为“了解发病机制和治疗阿尔茨海默病的新方法”的 P01 提案中
疾病”,我们寻求更好地了解 AD 的异质发病机制及其发生机制
受载脂蛋白 (apo) E 同种型的影响 apoE4 等位基因是晚发型的主要遗传风险因素。
AD 与脑实质中淀粉样斑块沉积的增加密切相关
晚期血管淀粉样蛋白病理学;以及 Aβ 寡聚化增强也参与其中。
突触可塑性、葡萄糖代谢、线粒体功能和血管完整性目前还没有。
关于不同 apoE 基因型如何影响 AD 发病机制的共识。
本 P01 的三个项目中提出的内容将有助于阐明 apoE 在 AD 中的复杂作用,因此本 P01 是。
我们提出一项综合的、多学科的研究工作,以解决一个具有重要意义的问题。
汇集了具有丰富成功合作历史的研究人员,他们在以下领域拥有专业知识
不同领域,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 的帮助下)以及常见 AD 模型的使用和
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 研究者开发的 µMRI 方法的生物标记技术,以确保协同作用
所有 P01 研究的科学研究将由生物统计学和生物信息学核心确保。
(核心 D)该 P01 的三个项目重点关注载脂蛋白 E (apoE) 同工型的差异作用。
发挥作用:1) AD 斑块和血管淀粉样蛋白的发育,通过整个过程的无偏见蛋白质组学评估
AD 病理学谱(项目 1);针对 Aβ/apoE 相互作用的创新治疗方法
(项目 2);和 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)预计将加强我们对不同影响的理解。
apoE 同种型对 AD 发病机制的影响,并加速发现有效的治疗方法
解决这些不同的角色。
项目成果
期刊论文数量(0)
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科研奖励数量(0)
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THOMAS M WISNIEWSKI其他文献
THOMAS M WISNIEWSKI的其他文献
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{{ truncateString('THOMAS M WISNIEWSKI', 18)}}的其他基金
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:
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:
10621848 - 财政年份:2020
- 资助金额:
$ 239.89万 - 项目类别:
Alzheimer's Disease Research Center- Supplement 3.2- Mark Bernard 2022
阿尔茨海默病研究中心 - 补充 3.2 - 马克·伯纳德 2022
- 批准号:
10610048 - 财政年份:2020
- 资助金额:
$ 239.89万 - 项目类别:
Alzheimer's Disease Research Center- Supplement 3.1- Anthony Briggs 2022
阿尔茨海默病研究中心 - 补充 3.1 - 安东尼·布里格斯 2022
- 批准号:
10610057 - 财政年份:2020
- 资助金额:
$ 239.89万 - 项目类别:
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