The definitive diagnosis of Alzheimer's disease (AD) can only be reached through the microscopic investigation of brain tissue. The Neuropathology Core will establish an infrastructure for timely autopsies and for the microscopic investigation of brain specimens from the control and dementia subjects enrolled in the Clinical Core of the ADCC. The Core will also accept control and dementia specimens from a cohort of neuropsychologically investigated subjects who are enrolled in a brain endowment program coordinated by the NIH-funded University of Miami Brain Endowment Bank. The tissue will be processed in a manner that allows systematic and uniform diagnostic procedures with traditional stains as well as more quantitative determinations of tangle density, amyloid burden, synaptic density and the integrity of selected transmitter pathways with the help of sensitive immunohistochemical procedures. Tissue will also be stored in unfixed-frozen, fixed-unembedded, fixed- paraffin-embedded, and fixed-and-frozen-sectioned form. These various combinations have been chosen in order to address the wide spectrum of requirements described by the 22 investigators at Northwestern University who plan to use the resources of the Neuropathology Core for their research. The investigation of all specimens will include a broad anatomical survey that will allow relevant clinico-pathological correlations with the neuropsychological domains that will be assessed by the Clinical Core. Some of the specimens will be processed in whole-hemisphere sections in order to address the requirement of some research projects for extensive anatomical and cytoarchitectonic detail.
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