PROJECT SUMMARY (See instructions): The aims of the Neuropathology Core are to provide technical resources, laboratory facilities and professional expertise for the collection, diagnosis and storage of tissue obtained at autopsy from patients with dementia and control subjects studied in the Clinical Core, National Cell Repository for Alzheimer's Disease (NCRAD), the Late Onset Alzheimer Disease project (LOAD), other Alzheimer disease centers (ADCs), the frontotemporal dementia (FTD) project of the NINDS, Parkinson Research: the Organized Genetics Initiative (PROGENI), and academic institutions as well as families from the community including those referred by the Alzheimer's Association chapters. The Neuropathology Core will provide information about pathologic data to referring physicians and families as well as well-characterized tissue to basic researchers. In addition, the Core will be involved in continuing education to physicians, researchers, technicians and the community about new developments emerging from Alzheimer disease (AD) research. Our understanding of the clinical, pathologic and molecular aspects of AD and other dementias has advanced rapidly. Brain tissue of demented individuals must be studied for diagnostic and research purposes using a multidisciplinary approach. We have expanded our Dementia Laboratory for degenerative brain diseases and our tissue repository. The Core has contributed to the investigations of hereditary presenile dementias by (1) characterizing familial AD with mutations in the APP, and PSENI genes, (ii) characterizing the neuropathoiogic phenotypes of sporadic and hereditary prion diseases, (iii) characterizing the neuropathoiogic phenotypes of frontotemporal dementia associated with MAPT, granulin, TDP-43 (iv) discovering novel mutations in APP, PSENI, PRNP, MAPT, Granulin, TDP-43, Ferritin Light Polypeptide and Neuroserpin genes as well as unclassified forms of presenile dementia. We have expanded our mission integrating molecular technology to assist in the neuropathoiogic diagnosis. We are combining data obtained by neurohistology, immunohistochemistry and immunocytochemistry to recognize and characterize the localization and the antigenic profile of molecules that are important to the pathogenesis of dementia. These studies carried out in parallel with molecular analysis are fundamental to understand disease etiology and phenotypic heterogeneity. We consider this multidisciplinary approach to be the hallmark of the IADC Neuropathology Core and will aid us in providing a definitive diagnosis of dementing disorders.

RELEVANCE (See instructions): It is estimated that as many as 5 million Americans have AD. The Indiana Alzheimer Disease Center provides an environment and resources directed towards fostering and coordinating research and educational activities on AD and other dementing illnesses.