The Healthy Aging and Senile Dementia progam project Neuropathology Core C has the Specific Aims of: (1) Assigning final neuropathologic diagnoses to all HASD subjects who come to autopsy (goal 25 new brains per year); (2) Performing brain autopsies on HASD subjects who give permission to do so, and to collect, store and distribute postmortem cerebrospinal fluid (CSF) and frozen brain tissue to program and other approved investigators to support research; (3) Maintaining electronic databases of neuropathology information that relates to autopsy examination, diagnosis, and tissue banking, in coordination with the Clinical and Biostatistics Cores; (4) Detecting and quantifying the full range of neuropathologic lesions associated with preclinical and overt dementia (senile plaques, neurofibrillary tangles, neuropil threads, argyrophilic grains, Lewy pathology, neuron loss, synaptic loss, tauopathic lesions, gliosis, etc.); and (5) to conduct developmental research using new histopathologic markers to promote diagnosis and to provide mechanistic insight into the causes and expression of dementing disorders compared to normal healthy aging and nondemented persons with preclinical Alzheimer disease (preclinical AD) brain lesions. * The Core leader McKeel, assisted by Senior Investigator Price and a well trained technical staff, have equipped the laboratory to process fixed brain tissue into paraffin blocks, to section these blocks at 6-10 microns, and to stain them with a variety of routine and special stains that include three silver methods (including Gallyas), thioflavine S, axon (modified Bielschowsky), and myelin stains (LFB-PAS). Immunohistochemical techniques are in place to detect a-beta amyloid, PHF type hyperphosphorylated tau, an Abeta-PHFtau dual stain to identify neuritic plaques with certainty, alpha-synuclein for synapses and Lewy pathology (neurites, pale bodies, brainstem and cortical Lewy bodies), ubiquitin, GFAP for astrocytic intermediate filaments, NeuN for neuron labeling, and synaptophysin for synapses. Dr. Price's laboratory will prepare 50 micron frozen sections of cytoarchitectonically defined brain regions (hippocampus, entorhinal cortex, cingulate cortex, gyrus rectus) for neuron counting using the Zeiss C.A.S.T. system. * This Core directly supports Projects 1-4 through it's Specific Aims, especially Aims 1, 3 and 5. Core brain lesion data will complement data obtained by the Clinical, Psychometric and Neuroimaging Cores.
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