Massachusetts Alzheimer's Disease Research Center

项目总结： 获奖项目是马萨诸塞州阿尔茨海默病研究中心。一把钥匙， 该中心的授权部分是一个神经病理核心，其使命是提供 尸检诊断并向调查人员提供组织，以推进 了解阿尔茨海默氏症及相关疾病。特定的组织制剂根据不同的情况而不同 科学项目。大体上，组织要么固定，要么嵌入石蜡块中 组织学分析，或快速冷冻并储存在零下80摄氏度。如果冷冻，组织可以 整块分布，用于均质和生化分析，或切成薄片 10微米厚度的数量级使用一种特殊的设备，低温恒温器，它可以 保持组织的冰冻状态，同时刮掉表面的切片。这些单薄 冰冻切片是实验的理想选择，如原位PET配体放射自显影 杂交、特异性免疫染色方案、构象特异性分析 蛋白酶消化、激光捕获显微切割和较新的分析方法，如原位测序。 尽管中心调查人员是这些方法的领导者之一(例如，我们的中心是 第一个发表了当代tau PET配体的放射自显影)，并拥有 使用其他命名技术的几个活跃的资助协议，我们已经 无法满足低温恒温器准备组织的要求，因为我们的低温恒温器无法维护 冰冻的温度，无法修复。 多年来，我们一直可以使用低温恒温器来制备冰冻切片 储存组织以便分发给调查人员。这些是徕卡CM 1900-6-1和Lecia CM 1900-3-1低温恒温器；两者都已超过18岁，不再起作用，也不能再 被维修或修理。因此，我们不能为上述高级研究准备样本。 以上包括激光捕获显微镜、原位杂交、原位测序、 受体/蛋白质聚合放射自显影。我们选择了徕卡CM 3050，这是 该设备的当前型号，以取代损坏和过时的低温恒温器。 总而言之，我们要求资金为我们的神经病理核心更换一台关键设备 ADRC的成员。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.