Massachusetts Alzheimer's Disease Research Center

马萨诸塞州阿尔茨海默病研究中心

• 批准号: 10511260
• 负责人: BRADLEY T. HYMAN
• 金额: $ 5.04万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-15 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10511260
• 关键词: 18 year old; Alzheimer' s Disease; Autopsy; Autoradiography; Award; Biochemical; Biological Assay; Diagnosis; Digestion; Drug or chemical Tissue Distribution; Equipment; Freezing; Frozen Sections; Funding; Generations; Histologic; In Situ Hybridization; Lasers; Ligands; Massachusetts; Microscopy; Microtomy; Mission; Modeling; Molecular Conformation; Names; Paraffin; Peptide Hydrolases; Positron-Emission Tomography; Preparation; Procedures; Protocols documentation; Publishing; Research; Research Personnel; Sampling; Services; Slice; Sum; Surface; Techniques; Temperature; Thick; Thinness; Tissue Banks; Tissues; cryostat; experimental study; in situ sequencing; laser capture microdissection; neuropathology; protein aggregation; receptor; repaired; tau Proteins; tissue preparation

Project summary: The awarded project is the Massachusetts Alzheimer Disease Research Center. A key, mandated component of this Center is a Neuropathology Core, whose mission is to provide autopsy diagnoses and provide tissue to investigators to further the overall mission of understanding Alzheimer’s and related illnesses. Specific tissue preparations vary according to the scientific project. Broadly, tissue is either fixed and embedded in paraffin blocks for histological analyses, or snap frozen and stored at -80 degrees C. If frozen, the tissue can be distributed en block for homogenization and biochemical analyses or cut into thin sections on the order of 10 microns thickness using a specialized piece of equipment, a cryostat, that can maintain the tissue in its frozen state while shaving the sections from the surface. These thin frozen sections are ideal for experiments such as autoradiography of PET ligands, in situ hybridization, specific immunostaining protocols, conformation specific assays including protease digestions, laser capture microdissection, and newer assays such as in situ sequencing. Although Center investigators are among the leaders in these approaches (eg. our Center was the first to publish autoradiography of the current generation of tau PET ligands), and have several active funded protocols in place using the other named techniques, we have been unable to fulfill requests for cryostat prepared tissues since our cryostat is unable to maintain freezing temperatures, and is unable to be repaired. We have had, for many years, access to cryostats for the preparation of frozen sections of banked tissue for distribution to investigators. These were a Leica CM 1900-6-1 and a Lecia CM 1900-3-1 cryostat; both are more than 18 years old, are no longer functional, and can no longer be serviced or repaired. We therefore cannot prepare samples for the advanced studies noted above including laser capture microscopy, in situ hybridization, in situ sequencing, receptor/protein aggregate autoradiography. We have chosen the Leica CM 3050, which is the current model of this equipment, to replace the broken and out of date cryostat. In sum, we request funds to replace a critical piece of equipment for our Neuropathology core of the ADRC. We appreciate your considering this request.

项目概要： 获奖项目是马萨诸塞州阿尔茨海默病研究中心， 该中心的法定组成部分是神经病理学核心，其使命是提供 尸检诊断并向调查人员提供组织以进一步完成 了解阿尔茨海默病和相关疾病的具体组织准备因人而异。 从广义上讲，组织被固定并嵌入石蜡块中。 组织学分析，或速冻并保存在 -80 摄氏度。如果冷冻，组织可以 分布成块用于均质化和生化分析或切成薄片 使用专用设备（低温恒温器）获得 10 微米的厚度， 保持组织处于冷冻状态，同时从表面刮取切片。 冰冻切片非常适合 PET 配体放射自显影、原位实验等实验 杂交、特异性免疫染色方案、构象特异性测定，包括 蛋白酶消化、激光捕获显微切割以及原位测序等较新的检测方法。 尽管中心研究人员是这些方法的领导者（例如，我们的中心是 第一个发表了当前一代 tau PET 配体的放射自显影术），并已 使用其他命名技术的几个积极资助的协议，我们一直在 无法满足对低温恒温器准备的组织的要求，因为我们的低温恒温器无法维持 冰点温度，无法修复。 多年来，我们一直可以使用低温恒温器来制备冷冻切片 储存的组织用于分发给研究人员，这些是 Leica CM 1900-6-1 和 Lecia CM。 1900-3-1 低温恒温器；均超过 18 年，不再起作用，并且不能再使用 因此，我们无法为上述高级研究准备样品。 以上包括激光捕获显微镜、原位杂交、原位测序、 我们选择了 Leica CM 3050，它是受体/蛋白质聚集体放射自显影仪。 该设备的当前型号，用于更换损坏和过时的低温恒温器。 总之，我们请求资金来更换神经病理学核心的关键设备 我们感谢您考虑这一请求。