Massachusetts Alzheimer's Disease Research Center

项目概要： 获奖项目是马萨诸塞州阿尔茨海默病研究中心。一把钥匙 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，并为调查人员提供组织，以促进整体使命 了解阿尔茨海默氏症和相关疾病。具体的组织制备根据 科学项目。广义地说，组织被固定并包埋在石蜡块中， 组织学分析，或快速冷冻并储存在-80 ℃。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， 10微米厚度的数量级，使用专门的设备，低温恒温器，可以 保持组织处于冷冻状态，同时从表面剃掉切片。这些薄 冷冻切片是理想的实验，如PET配体的放射自显影，在原位 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、激光捕获显微切割和较新的测定，如原位测序。 虽然中心的研究人员是这些方法的领导者之一（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），并且具有 几个积极资助的协议到位使用其他命名的技术，我们已经 由于我们的低温恒温器无法维持，因此无法满足低温恒温器制备组织的要求 温度极低，无法修复。 多年来，我们一直使用低温恒温器来制备冷冻切片， 储存组织以分发给研究者。这是一个徕卡CM 1900-6-1和一个莱卡CM 1900-3-1低温恒温器;两者都超过18岁，不再起作用，并且不能再 维修或修理。因此，我们无法为上述高级研究准备样本 包括激光捕获显微术，原位杂交，原位测序， 受体/蛋白聚集体放射自显影。我们选择了Leica CM 3050， 该设备的当前型号，以取代破碎和过时的低温恒温器。 总而言之，我们申请资金来更换我们神经病理学核心的关键设备 在ADRC。我们感谢您考虑这一请求。

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.