CORE-- NEUROPATHOLOGY

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The Neuropathology Core of the UC Davis Alzheimer's Disease Center (UCD ADC) has 3 major goals: (1) to obtain brain autopsies on ADC patients and controls, (2) to accurately diagnose all brain lesions encountered at autopsy in these individuals and transfer information about these diagnoses to the clinical core, and (3) to preserve and distribute autopsy brain tissues to research collaborators. This Core has developed a protocol in conjunction with the Clinical Core for recruitment of subjects to the brain donation program which relies upon ADC clinicians to approach patients or controls early on in the evaluation process. Once recruited, a number of methods have been developed for the distribution and tracking of signed autopsy consents and procedural information so that, at the time of death, the mechanism for activating the brain retrieval protocol is simple and straightforward. This protocol relies upon 24-hour a day on-call trained technicians who travel to the local mortuary (or other facility) to remove the brain. In most cases, half the brain is formalin fixed and the other half is coronally sectioned and frozen between dry ice. In special situations such as cerebrovascular disease, advance information is provided about lesion location so that the relevant area is formalin fixed. Provisions for very rapid brain removal and tissue processing are also made for some collaborators. Subsequent processing is performed in the Neuropathology Core Laboratory in Davis. Initially, 25 blocks of formalin fixed tissue will be obtained for paraffin embedment from multiple neocortical, limbic, diencephalic, basal ganglia, and brainstem regions. All sections will be stained with hematoxylin-eosin and a subgroup with Bielschowsky's sliver technique. Selected blocks will be stained with Luxol fast blue-cresyl violet to identify periventricular white matter degeneration, and with Congo red and beta amyloid immunostain to detect associated amyloid angiopathy. The blocks taken are compatible with those suggested by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD). All tissue will be examined by a single neuropathologist, the Core PI, who will produce a standard gross and microscopic neuropathology report, and will quantitate neuritic plaques and neurofibrillary tangles. This method permits classification of all pathological diagnoses according to the suggested CERAD schema. Final reports are returned to the Clinical Core, where they are communicated to the patient's next of kin by ADC clinicians familiar with the case. Tissue and brain DNA is banked in the neuropathology laboratory. mRNA screening of frozen specimens will be used to assess the acceptability of tissue for molecular and biochemical studies. All data are logged into the Neuropathology Laboratory data base, which includes an inventory of all tissue, mode of processing and storage, pathological diagnosis, and autolysis interval. Quantitative data and final neuropathologic diagnoses according to CERAD criteria are recorded and entered into the centralized database, where it is readily linked to other data.