TISSUE, PEPTIDE AND GENETICS RESOURCE CORE

组织、肽和遗传资源核心

• 批准号: 9256399
• 负责人: Wayne W Poon
• 金额: $ 28.45万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9256399
• 关键词: Alzheimer' s Disease; Alzheimer' s disease risk; Amyloid; Amyloid beta-Protein; Animal Model; Antibodies; Autopsy; Biological; Biological Assay; Biological Models; Blood; Blood Vessels; Brain; Cell model; Clinical; Clinical Data; Cognitive; Collaborations; DNA analysis; Data; Data Set; Databases; Dementia; Equipment and supply inventories; Fibroblasts; Functional disorder; Genes; Genetic; Goals; Human; Impairment; Individual; Inflammation; Inflammatory; Instruction; Knowledge; Late Onset Alzheimer Disease; Lead; Measurement; Memory impairment; Molecular Models; Neurobiology; Neurodegenerative Disorders; Neuronal Plasticity; Neuropsychological Tests; Outcome Study; Pathogenesis; Pathway interactions; Peptide antibodies; Peptides; Play; Preparation; Process; Program Accessibility; Program Research Project Grants; Proteins; Reagent; Research; Research Personnel; Research Project Grants; Research Support; Resources; Risk Factors; Sampling; Single Nucleotide Polymorphism; Specimen; Standardization; Synapses; Synaptic plasticity; Tissues; Translating; aged; behavioral plasticity; data integration; genetic information; genetic resource; genome wide association study; healthy aging; high throughput analysis; improved; individual patient; induced pluripotent stem cell; innovation; mental state; molecular modeling; neuroinflammation; neuron loss; neuropathology; non-demented; programs; protein transport; risk variant; tau Proteins

Core B: Tissue, Peptide and Genetics Resource Core This program project is broadly focused on understanding the mechanisms by which inflammation modulates AD pathogenesis. An additional theme of this project is focused on how proteins recently identified by Genome Wide Association Studies (GWAS) in Alzheimer disease (AD) modulate the infiammatory cascade, contribute to endocytic dysfunction, and impair protein trafficking/clearance, and thereby increase AD risk. An overarching goal of the program project is to utilize molecular, cellular and animal model systems to identify and characterize mechanisms and pathways associated AD neuropathology (e.g. Aß, tau, inflammation, and synaptic and neuronal loss) and neuroinflammation. The outcome of these studies can be translated and verifled in human autopsy brain specimens. The Tissue, Peptide, and Genetics Core plays a key role in support of the program project research goals. To achieve these goals, the Tissue, Peptide and Genetics Core has four aims. (1) Produce and provide well-characterized, high quality peptides, antibodies, and Aß assays to individual investigators. All program investigators require either Aß peptides, preparations of different types of Aß assembly states, or both soluble and insoluble Aß measurements. (2) Carry out high- throughput analysis for newly identified single nucleotide polymorphism (SNP) risk alleles for late-onset AD to support investigator research. Individual investigators will require SNP data from living subjects, from induced pluripotent stem cells derived from fibroblasts, as well as from brain autopsy specimens. (3) The Tissue, Peptide, and Genetics Core will support program project research by providing dedicated high quality clinically and neuropathologically characterized human autopsy and biological specimens (blood, fibroblasts) for use by program project investigators (including SNP data from GWAS-identified AD-risk genes). (4) Coordinate and maintain a database of quantitative variables and of resource use to be shared among program investigators. The Core collates and integrates quantitative neurobiological and clinical data, which will be provided to investigators to allow the seamless integration of data from individual research projects

核心B：组织、多肽和遗传学资源核心 这个项目主要集中在了解炎症调节的机制。 AD发病机制。这个项目的另一个主题是关注最近如何通过 阿尔茨海默病(AD)的全基因组关联研究(GWAS)调节炎症级联反应， 导致内吞功能障碍，损害蛋白质的运输/清除，从而增加AD的风险。 该计划项目的首要目标是利用分子、细胞和动物模型系统 识别和描述与AD神经病理相关的机制和途径(例如，A？、tau、 炎症、突触和神经元丢失)和神经炎症。这些研究的结果可以是 在人类尸检脑标本中进行翻译和验证。组织、多肽和遗传学核心发挥着作用 在支持计划项目研究目标方面发挥关键作用。为了实现这些目标，组织、多肽和 遗传学核心有四个目标。(1)生产和提供具有良好特性的高质量的多肽、抗体、 A？对个人调查人员进行化验。所有项目调查人员都需要A？多肽、制剂 不同类型的A？集合态，或同时测量可溶和不可溶的A？(二)实行高标准 新发现的晚发性AD单核苷酸多态(SNP)风险等位基因的吞吐量分析 以支持调查员的研究。个人调查人员将要求从活着的受试者那里获得SNP数据 诱导的多能干细胞来自成纤维细胞，以及来自脑尸检标本。(3) 组织、肽和基因核心公司将通过提供专门的高质量支持计划项目研究 临床和神经病理学特征的人类尸检和生物标本(血液、成纤维细胞) 供计划项目调查人员使用(包括来自GWAS确认的AD风险基因的SNP数据)。(4) 协调和维护量化变量数据库和资源使用数据库，以供 项目调查员。该中心整理和整合量化的神经生物学和临床数据， 将提供给调查人员，以便无缝集成来自各个研究项目的数据