This core provides specialized services, required by at least three of the four projects ofthe PPG. These services are best coordinated by a core to increase efficiencies of time and cost, promote scientific synergies, and maximally utilize dedicated highly specialized facilities. This PPG is a multidisciplinary investigation of in vivo and in vitro models of endosomal, autophagic, and lysosomal abnormalities in Alzheimer's disease (AD) considered critical to AD pathogenesis. Core C acquires or generates critical reagents, eg. 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 (brains and fibroblasts) from cases of AD, FAD, Trisomy 21 and non-demented and non-AD neurological controls in a coordinated manner for studies in the PPG. Cultured primary mouse neurons prepared under standardized conditions will be distributed routinely. 2. To perform electron microscopy and immunogold electron microscopy on cell and mouse models and human brains. 3. To perform ELISA measurements of Abeta 40 and Abeta 42 to quantify endogenous murine Abeta and human Abeta in AD brains, brains of mouse models and media and lysates of fibroblasts and other cell models. 4. To provide specialized histological procedures, fluorescence/confocal applications, morphometric techniques and neurosurgical procedures as needed for all four projects 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 anfibodies. 6. To administer to mouse models behavioral assays of memory and motor performances from a highly standardized battery of validated tests. The Core serves all projects and is essential to their success.
This Core provides well-characterized biological materials and standardized state-of-the-art technical services needed to perform the studies in this PPG, which aims to understand how AD develops and will identify new directions for the therapy of AD and possibly other aging-related neurodegenerative diseases.
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