TISSUE, PEPTIDE AND GENETICS RESOURCE CORE

组织、肽和遗传资源核心

• 批准号: 8882193
• 负责人: Wayne W Poon
• 金额: $ 27.59万
• 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/8882193
• 关键词: Alzheimer' s Disease; Alzheimer' s disease risk; Amyloid; Animal Model; Antibodies; Autopsy; Behavioral; Biological; Biological Assay; Biological Models; Blood Vessels; Blood specimen; Brain; Cell model; Clinical; Clinical Data; Cognitive; Collaborations; DNA; Data; Data Set; Databases; Dementia; Equipment and supply inventories; Fibroblasts; Functional disorder; Genes; Genetic; Goals; Human; Individual; Inflammation; Inflammatory; Instruction; Knowledge; Late Onset Alzheimer Disease; Lead; Life; Measurement; Memory; Molecular Models; Neurobiology; Neurodegenerative Disorders; Neuronal Plasticity; Neuropsychological Tests; Outcome Study; Pathogenesis; Pathway interactions; Patients; Peptide antibodies; Peptides; Play; Polymorphism Analysis; Preparation; Process; Program Research Project Grants; Proteins; Reagent; Research; Research Personnel; Research Project Grants; Research Support; Resources; Risk Factors; Sampling; Single Nucleotide Polymorphism; Specimen; Staging; Synapses; Synaptic plasticity; Tissues; Translating; aged; data integration; genetic information; genetic resource; genome wide association study; healthy aging; high throughput analysis; improved; induced pluripotent stem cell; innovation; mental state; molecular modeling; neuroinflammation; neuron loss; neuropathology; 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、肽和遗传资源核心 这个项目主要集中在了解炎症调节的机制 AD发病机制该项目的另一个主题是关注最近通过 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，并损害蛋白质运输/清除，从而增加AD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， 识别和表征与AD神经病理学相关的机制和途径（例如，Ablad 3，tau， 炎症以及突触和神经元损失）和神经炎症。这些研究的结果可能是 翻译并在人类尸检大脑标本中验证。组织、肽和遗传学核心发挥着 支持项目研究目标的关键作用。为了实现这些目标，组织，肽和 遗传核心有四个目标。(1)生产和提供表征良好的高质量肽，抗体， 和Aprilate测定。所有项目研究人员都需要使用阿托伐他汀肽， 的不同类型的Ablation组装状态，或可溶性和不溶性Ablation测量。(2)执行高- 新鉴定的晚发性AD的单核苷酸多态性（SNP）风险等位基因的通量分析 以支持调查员的研究。个体研究者将需要来自活体受试者、来自 诱导多能干细胞来源于成纤维细胞，以及来自脑尸检标本。(3)的 组织，肽和遗传学核心将通过提供专门的高质量支持计划项目研究 具有临床和神经病理学特征的人体尸检和生物标本（血液、成纤维细胞） 供项目研究者使用（包括来自GWAS鉴定的AD风险基因的SNP数据）。（四） 协调和维持一个数量变量和资源使用数据库，供各机构共享。 项目调查员。核心整理和整合定量神经生物学和临床数据， 将提供给研究人员，以便无缝整合来自各个研究项目的数据