application): The UCI Neuropathology Core provides the Clinical Core with definitive neuropathological diagnoses of patients who come to autopsy and serves to link clinical research with basic research. As part of the proposed ADRC, the core will also be supporting 3 of the 4 projects by providing tissues and peptides to 2 projects (Glabe and Tenner) and the final neuropathological diagnosis to the third project (Batchelder). The investigators are prepared to handle a projected 45 cases per year. An average post-mortem delay of 3.8 hours is achieved by rotating two staff members on 24-hr pager duty. Diagnoses are made based on the recently developed criteria from the NIA-Reagan working group and cases are evaluated by two pathologists. A random set of cases (5%) will be shared with Dr. Carol Miller for quality assurance. The Core accepts only cases that have been clinically assessed. Clinical diagnostic accuracy has been 88% over the last 5 years. The Neuropathology Core will continue to maintain a tissue repository of CSF, serum, and formalin, paraformaldehyde, or frozen tissues, as well as specially prepared sections for stereology and electron microscopy. The Core has already provided Dr. Glabe?s project with specially fixed tissue to generate the EM preliminary data and has provided Dr Tenner?s project with tissues from clinically assessed Down s cases. Since 1984, the tissue repository has processed over 675 cases. In the past five years, resources from this Core have been distributed to over 80 investigators at 39 different institutions and have resulted in over 120 publications. Tissues are primarily obtained from patients enrolled in the Clinical Core, and consist of those with probable AD, those with early signs of dementia, and control individuals in the """"""""Successful Aging Program"""""""". A more detailed analysis of neuropathology for research purposes includes quantification of specific variables (e.g. Braak stage, ApoE genotype, beta-amyloid and PHF/tau """"""""loads"""""""", and plaque and neurofibrillary tangle counts via image analysis). Neuropathological quantification of each case permits validation and continued refinement of clinical diagnoses, assists the staff in selecting cases for research studies, and may facilitate early detection, identification of subtypes, or targeting therapeutic interventions to similar cases who are still alive. All neuropathological data are entered into a database and are linked to clinical data, diagnosis, tissue inventories and allocation. In addition, the Neuropathology Core will produce and provide synthetic beta-amyloid peptide derivatives for ongoing and future investigations of beta-amyloid associated molecular events related to AD pathology and for the quantification of pathology.
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