ANALYTICAL CORE

分析核心

• 批准号: 6920484
• 负责人: RALPH A. NIXON
• 金额: $ 22.89万
• 依托单位: NATHAN S. KLINE INSTITUTE FOR PSYCH RES
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6920484
• 关键词: Alzheimer' s disease; Downs syndrome; Niemann Pick disease; antibody; autophagy; biomedical facility; cell line; cellular pathology; confocal scanning microscopy; electron microscopy; endocytosis; enzyme linked immunosorbent assay; fluorescence microscopy; histology; immunoelectron microscopy; immunologic substance development /preparation; liquid chromatography mass spectrometry; longitudinal animal study; lysosomes; magnetic resonance imaging; molecular pathology; morphometry; neuropathology; sample collection; tissue resource /registry; training; video microscopy

This core provides specialized services required for all four projects of the PPG. These are best coordinated by a core to increase efficiencies of time and cost, promote scientific synergies, and maximally utilize dedicated highly specialized facilities. This program grant is a multidisciplinary investigation of in vivo and in vitro models of endosomal, autophagic, and lysosomal abnormalities in AD considered critical to AD pathogenesis. Neuropathological assessment and biochemical quantification of AD pathologies in these models is a major goal of the core. Other core functions are the maintenance of critical reagents (antibodies and cell lines) that are used in every project and must be maintained under rigorously controlled conditions to allow reliable comparisons of information across projects. The specific aims are: 1. To acquire, store and efficiently distribute well-characterized tissues (brain and fibroblasts) from cases of AD, FAD, Trisomy 21 and non-demented and non-AD neurological controls in a coordinated manner for studies in all four projects. 2. To perform electron microscopy and immunogold electron microscopy on cell and mouse models and human brain. 3. To perform ELISA measurements of Ab40 and Ab42 to quantify endogenous murine Ab and human Ab in AD brain, brains of mouse models, medium and lysates of fibroblasts and other cell models, and, when appropriate, to perform liquid chromatography-mass spectroscopy to identify Ab peptides and peptide cleavage sites on APP metabolites. 4. To provide specialized histological procedures and morphometric techniques as needed to characterize neurodegeneration and other AD pathologies as well as provide training on laser confocal microscopy and video-fluorescent microscopy. 5. To maintain and distribute polyclonal and monoclonal antibodies and generate additional polyclonal antibodies as necessary. 6. In years 08-10 of the PPG, to provide in vivo functional MRI analysis for selected animal models to characterize alterations in pathology longitudinally. The core serves all projects and is essential to their success.

该核心提供了PPG所有四个项目所需的专业服务。这些最好由核心协调，以提高时间和成本的效率，促进科学协同作用，并最大程度地利用专用的高度专业设施。该计划的赠款是对体内和体外模型的多学科研究，在被认为对AD发病机理至关重要的AD中，内体，自噬和溶酶体异常。这些模型中AD病理学的神经病理学评估和生化量化是核心的主要目标。其他核心功能是维护每个项目中使用的关键试剂（抗体和细胞系），必须保持在严格控制的条件下 允许跨项目的可靠比较信息。具体目的是：1。从AD，FAD，FAD，21，三体术以及非痴呆和非AD神经系统控制的情况下以协调的方式进行研究，以在所有四个项目中进行研究，从而从AD，FAD，21，非痴呆和非AD神经系统控制中获取，存储和有效分布良好的组织（脑和成纤维细胞）。 2。在细胞，小鼠模型和人脑上执行电子显微镜和免疫元电子显微镜。 3。执行AB40和AB42的ELISA测量以量化内源鼠AB和人类 AB在AD大脑中，小鼠模型，成纤维细胞和其他细胞模型的介质和裂解物的大脑，以及在适当的情况下进行液相色谱 - 质谱光谱法，以鉴定ABS代谢物上的AB肽和肽裂解位点。 4。根据需要提供专门的组织学程序和形态计量学技术来表征神经变性和其他AD病理学，并提供有关激光共聚焦显微镜和视频荧光显微镜的培训。 5。维持和分布多克隆和单克隆抗体并根据需要生成其他多克隆抗体。 6。in PPG的08-10年，为选定动物模型提供体内功能性MRI分析，以纵向表征病理的改变。核心为所有项目提供服务，对其成功至关重要。