The Neuropathology Core C will provide neuropathologic diagnostic service for all program project subjects who come to autopsy. The CERAD neuropathology protocol will be used to assess general neuropathogic findings. The NIA/AARP quantitative diagnostic criteria will be used to establish a pathologic diagnosis of Alzheimer's disease (AD). The Core will use quantitative manual and automated computer-assisted morphometric methods to determine patterns, prevalence and severity of neuron atrophy and loss and NP and NFT accumulation associated with aging, AD, and AD-associated with Parkinsonism. Multivariate statistics will be used to correlate pathologic lesions with clinical and psychometric measures, especially important in mild dementia. The Core will process an estimated 25 brains annually. We will provide neuropathologic documentation of specific lesions and diseases in our aging and demented and nondemented aged samples. WE will provide the data for validation of clinical diagnostic criteria for subjects in Project 1 (intellectual function and Alzheimer changes in the very old), Project 3 (SDAT and Parkinsonism), Project 4 (memory processing in aging and dementia), Project 5 (lay interviewer assessment), Project 7 (neuroanatomical markers), and Project 8 (PET in aging and SDAT). Histologic criteria for differentiation of healthy aging and AD in the very old will be clarified. The neuropathological basis of parkinsonism in AD will be clarified. The hypothesis that parkinsonian dementia is due to SDAT-like neuropathology will be tested. By studying cases of mild SDAT and counting neuritic plaques by subtypes, we will test the additional hypothesis that purely fibrillary plaques are precursors to classical plaques with expanded neurites and amyloid cores. Our studies will identify how hippocampal, basal forebrain and neocorticallesions are related to dementia in AD. The relevant material for this effort includes those healthy control subjects enrolled in the Clinical Core who come to autopsy in the stages of very mild dementia.
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