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 We have chosen the Leica CM 3050, which is the current model of this equipment, to replace the broken and out of date cryostat.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.