Brain Tissue Processing and Neuropathological Evaluation of Specimens Obtained by the Alzheimer’s Disease and Schizophrenia Brain Bank

Histologic Methods

Representative blocks are taken from the following regions and are submitted for paraffin embedding and histologic examination: 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 mammillary bodies, thalamus, midbrain, pons, medullar, cerebellar vermis, and lateral cerebellar hemisphere. Sections from paraffin embedded blocks are stained using the following methods: hematoxylin and eosin, modified Bielschowski, modified thioflavin S, anti-b amyloid, and anti-tau. Any case showing evidence of Lewy body formation in the substantia nigra or locus ceruleus undergoes anti-ubiquitin staining of representative cerebral cortical sections for the identification of cortical Lewy bodies. Immunohistochemical procedures employ an avidin-biotin staining procedure with diaminobenzidine detection.

Neuropathology Data Collection

All neuropathology data regarding the extent and distribution of neuropathologic lesions is collected in a blind fashion. That is, the neuropathologists are not aware of any of the clinical and psychometric data while evaluating the slides for the presence and extent of relevant neuropathologic lesions. Every case is evaluated for the extent of neuropathologic lesions using the CERAD (Mirra et al. The Consortium to Establish a Registry for Alzheimer's Disease [CERAD]. Part II. Standardization of the neuropathologic assessment of Alzheimer's disease. Neurology 41: 479-486) neuropathologic battery. The CERAD data-base includes regionally specific semi-quantitative measures of total senile plaques, plaques with amyloid cores, neurofibrillary tangles, parenchymal and leptomeningeal vascular amyloid accumulation, Lewy bodies, Hirano bodies, granulovacuolar degeneration, Pick bodies, and global measures of neuronal loss and gliosis. Semi-quantitative ratings for neuritic threads as well as an additional anatomic site for lesion rating, namely the inferior temporal cortex (area 20), have been added to the CERAD battery. Additionally, quantitative data regarding the density of senile plaques in the mid-frontal gyrus, orbital frontal cortex, superior temporal gyrus, inferior parietal cortex, and calcarine cortex are collected.

Diagnostic Neuropathology Evaluation

After all of the above data regarding the extent and distribution of relevant neuropathologic lesions are collected and entered in the data-base individual cases undergo diagnostic neuropathology evaluation. For this process all clinical, neuropsychological, and laboratory data are evaluated. Each diagnosis is accompanied by a diagnostic narrative that incorporates all of the clinical, neuropsychological, and other medical aspects of each individual case.