The Neuropathology Core of the Alzheimer's Disease Center (ADC) will 1) supervise the acquisition ob brain tissue from patients 50 years of age and over who die and have autopsy consent given and 2) undertake the neuropathologic analysis of these cases over 5 years. We will 1) autopsy 100 demented patients and cognitively intact elderly controls per year and 2) take brain specimens according to one of four protocols. Thirty of these autopsies will be performed in cases with neuropathologic lesions exclusively limited to Alzheimer's disease (AD) or in neuropathologically normal controls and will be dissected using the full dissection protocol. In view of difficulties in obtaining brain samples from early stages (o.5, 1.0), presenile cases (under 65 years of age), and rapidly progressive AD, we will prioritize these cases for acquisition under the full dissection protocol. For those subject groups for which we have abundant samples in our Brain Bank (senile, severe, slowly progressive), we will take tissue samples using the limited dissection protocol (50 cases per year). In view of the inclusion of the Rural Satellite cases, and the need for private pathologists in those areas to collect brains for us, we have also developed a simplified rural dissection protocol (10 cases per year) to provide both frozen and formalin-fixed samples. We will provide neuropathologic diagnoses on all patients enrolled in the Satellites, even if they are excluded from further studies. We also will 3) quantify the topographic extent of classical AD changes (neurons with neurofibrillary tangles (NFT) and senile plaques (SP) in neocortex and hippocampus) in these case using random sampling techniques. Additional demented patients (10 per year) will have multi-infarct demential (MID) and serve as a diseased non-AD control group. Finally, we will localize and quantify the amount of infarcted tissue in cases of multi-infarct dementia (MID) and assess the degree of concomitant AD, if present. The Brain Bank will 1) store the tissue not immediately used in the ADC or Leadership and Excellence in Alzheimer's Disease (LEAD) from the AD , control, and MID brains acquired by the Neuropathology Core and 2) distribute that tissue to investigators who have made approved requests. Secondly, the Brain Bank will also continue to store and distribute the unused tissue of the cases collected between 1984 and the present. There are three types of tissue available: 1) tissue of the left hemisphere stored in liquid nitrogen or at -80 degree C, 2) tissue of th right hemisphere stored in neutral buffered formalin at room temperature, and 3) serial frozen sections of the basal forebrain-diencephalon-basal ganglia and locus coeruleus in cryoprotectant stored at -20 degree C in freezers. The Brain Bank maintains a log of tissue to assist in determining availability of specific regions and in locating tissue. Also maintained is a record of the distribution of tissue to investigators. The procedures for requesting tissue and obtaining approval are described.
