The Neuropathology (NP) Core will perform diagnostic evaluations and quantitative analyses on brain tissue collected at autopsy of participants in the Mayo Alzheimer Disease Research Center (ADRC) and related projects, in particular the Alzheimer Disease Patient Registry (ADPR). These overall goals will be achieved with the following 7 specific aims: 1) Perform brain autopsies on participants of the Mayo ADRC in a timely fashion and according to protocol. 2) Provide neuropathologic evaluations and collect neuropathologic data for all brains using standardized neuropathologic methods for gross dissection and neurohistology. Traditional histological methods, using silver stains and CERAD scoring, will be performed on all cases. Perform immunostaining with antibodies to alpha-synuclein on all cases. In cases with Lewy bodies, they will be counted in cortical regions to assign a diagnostic category according to the Consortium on Dementia with Lewy Bodies criteria. Photograph and map vascular lesions on cases with vascular pathology. 3) Hold quarterly consensus clinicopathological conferences in Rochester to arrive at final clinicopathologic diagnoses. Conduct monthly videoconferences of the NP Core personnel to discuss problem cases and other issues related to the administrative function of the NP Core. 4) In Jacksonville frozen tissue samples will be studied with analytic methods to determine the amount of Abeta40, Abeta42, tau and synaptic markers in brain tissue. Immunohistochemical analysis of lesion burden will also be used on correlative projects [e.g., Project 1, PI Cliff Jack]. 5) Characterize non-Alzheimer dementias with immunocytochemistry and electron microscopy, and provide DNA and tissue samples on cases to Project 2 (PI Mike Hutton) for studies of biochemistry and genetics of non-Alzheimer dementias, especially the frontotemporal dementias. 6) Store brain tissue and brain derived material and provide clinically and pathologically well-characterized tissue samples for on-going research [e.g., Project 3, PI Steve Younkin] and pilot research projects at Mayo Clinic and qualified outside investigators. 7) Provide neuropathological data to the National Alzheimer Coordinating Center (NACC) and neuropathologic materials to collaborative projects that develop through the NACC.
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