After the subject's death, consent for autopsy was obtained from the next of kin. A member of the AD brain bank team extracted each brain and extensively photographed the specimen. Any gross abnormalities were noted, and the brain was divided in the midsagittal plane. The right hemisphere was then suspended from the basilar artery in 4% cold (4oC) buffered paraformaldehyde. The left hemisphere was further dissected and snap-frozen. All neuropathological studies were performed on the right hemisphere by 2 of us (D.P.P. and D.P.P.). In some subjects, the left hemisphere was also included for neuropathological study because of gross lesions or suspected neuropathological lesions due to the clinical presentation of specific subjects, but these subjects were excluded from consideration for the studies described herein. Neuropathological assessments were performed after 4 to 6 weeks of fixation. The neuropathological assessment consisted of examining representative blocks from superior and midfrontal gyrus, orbital cortex, basal ganglia with basal forebrain, amygdala, hippocampus (rostral and caudal levels with adjacent parahippocampal and inferior temporal cortex), superior temporal gyrus, parietal cortex (angular gyrus), calcarine cortex, hypothalamus with mamillary bodies, thalamus, midbrain, pons, medulla, cerebellar vermis, and lateral cerebellar hemisphere. Sections from paraffin-embedded blocks were stained using hematoxylin-eosin, modified Bielschowsky, modified thioflavine S, anti–β amyloid (4G8 [gift of N. Robakis, PhD, Mount Sinai School of Medicine]), and anti-tau (AD2 [gift of A. Delacourte, PhD, Unite INSERM 422, Lille, France]). Any subject showing evidence of Lewy body formation in the substantia nigra or locus ceruleus underwent antiubiquitin (Daka Corporation, Carpinteria, Calif) staining of representative cerebral cortical sections for the identification of cortical Lewy bodies. Immunohistochemical procedures used an avidin-biotin staining procedure with diaminobenzidine detection. All neuropathological data regarding the extent and distribution of neuropathological lesions were collected by neuropathologists unaware of any of the clinical and psychometric data. After all of these data regarding the extent and distribution of relevant neuropathological lesions were collected and entered into the research databases, individual subjects underwent diagnostic neuropathological evaluation. For this process, all clinical, neuropsychological, and laboratory data were evaluated, and a final neuropathological diagnosis was assigned to each subject.