The aims of the Neuropathology Core will be: 1. To make neuropathologic diagnoses on all new brain accessions from ADRC research subjects using standard diagnostic criteria where possible. The staging of Alzheimer's disease (AD) lesions will be assessed according to the protocols of Braak and Braak [9] and updated t o include an immunohistochemical assessment of lesions as proposed in 2006 [8]. Lewy body pathology will be rated according to the scheme proposed by Braak et al. [10] and McKeith et al. [28,27,26]. To ensure fidelity with the diagnostic criteria used for alI cases since 1985, we continue to use the neuropathologic diagnostic criteria of Khachaturian [22] for AD and also provide diagnoses in every case using criteria of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) [30] and the probabilistic criteria proposed by the National Institute on Aging and Reagan Institute [ 1]. ( See B. Background and Significance). 2. To perform brain autopsies and to collect, store at -80?C, and distribute fixed and frozen brain tissue samples to support ADRC projects and investigators and outside research collaborations. 3. To maintain a computerized neuropathology database in concert with the Data Management and Statistics (Core C) and the Clinical Core (B) and the Washington University Center for Biomedical Informatics (CBMI). Information stored will include macroscopic images of fresh and fixed brain, demographic data, diagnoses, semi-quantitative morphometric data, neuropathology reports (in collaboration with Dr Schmidt, Chair. Division of Neuropathology), bibliographic information, and data relevant to Core tissue banking activities. In addition, neuropathology data will be transferred, after Core C quality control and validation, to the National Alzheimer Coordinating Center (NACC), University of Washington, Seattle, WA (U01-AG016976). 4. To support Project 3 (role of APOE e3 and e4 proteins in AD) by providing tissue samples from 96 cases together with quantitative morphometric data including ABeta load and integrate with all aspects of the ADRC.
The Neuropathology Core is essential to establish the gold standard neuropathologic diagnosis for each participant who comes to autopsy. The neuropathologic diagnosis will be essential for determining the specificity and sensitivity of biomarkers (CSF, amyloid imaging) of early AD.
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