Sunhee C. Lee, MD - US grants

The major purpose of the Neuropathology Core (NP Core) is to perform diagnostic neuropathologic evaluations on brains of participants in the Einstein Aging Study (EAS). To accomplish this aim, the NP Core integrates its activities with the Einstein/Montefiore Pathology Departmental on-call service for harvesting brains of subjects enrolled in the EAS in a timely fashion and according to protocol. The NP Core uses standardized dissection and processing procedures and collects neuropathologic data from all brains with the following methods: a. Gross examination with digital photography, b. Assessment of histopathology, c. Lesion counts with thioflavin-S fluorescent microscopy, and d. PHF-tau immunostained sections for staging Alzheimer type pathology. For cases with vascular lesions, gross lesions are photographed and the number, type and distribution of lesions are documented. In cases with either neuronal loss or Lewy bodies in the substantia nigra, multiple sections are immunostained with antibodies to synuclein. The amygdala of all AD cases is screened for synuclein immunoreactive Lewy bodies and for 4-repeat tau immunoreactive argyrophilic grains. When detected, the density of Lewy bodies is determined in multiple cortical areas and the amygdala. Non-Alzheimer degenerative dementias are characterized with immunocytochemistry and antibodies to neurofilament, ubiquitin and PHF-tau. Microglial immunohistochemistry is also routinely used to demonstrate diverse pathologies. The NP Core provides fixed and frozen brain samples to Project 3 for immunocytochemical, image analytical and enzyme linked immunosorbent assays. Tissue is provided to other qualified investigators with approval of the Administrative Core. The NP Core determines apolipoprotein-E genotypes and TAU haplotypes and banks DNA and RNA from brain tissue. Tissue quality is also assessed with pH and western blots for HSP70. Tissue samples, slides and paraffin blocks are banked for future studies. Reports are provided to the Administrative Core and data to the Statistical Core using standardized protocols and procedures.

PROJECT SUMMARY/ABSTRACT The major purpose of the Neuropathology Core (NP Core) is to perform diagnostic neuropathologic evaluations on brains of participants in the Einstein Aging Study (EAS) and to support research for the Projects. The NP Core integrates its activities with the Montefiore Pathology Departmental on-call service for harvesting brains in a timely fashion of subjects enrolled in the EAS. The NP Core uses standardized dissection and processing procedures and collects neuropathologic data from all brains. Diagnostic reports are communicated with key personnel of the EAS as soon as they are completed by electronic communication. Clinicopathologic correlation analyses are discussed in person at annual meetings. The Specific Aims of the NP Core are as follows: Aim 1. Perform brain autopsies and prepare tissue for transport from Montefiore Hospital to Mayo Clinic. Aim 2. Diagnostic neuropathology using a standardized and systematic approach that has been used over the life of the EAS, permitting use of the entire autopsy cohort for clinicopathologic correlative studies and for use in research studies. Aim 3. Data entry from neuropathology report. A written report is generate in text form for easy communication with clinicians and family members, but a digital form is created for long-term storage and linkage to NP Core databases - one specific to the Einstein Aging Study and the other a part of the Mayo Clinic brain bank for neurodegenerative disorders, which is linked to tissue inventory, ancillary data (e.g., genetic data), as well as quantitative pathology and demographics, which permits pooling of Einstein Aging Study cases into larger clinicopathologic studies. Neuropathologic data are transferred to Biostatistics and Data Management Core. Aim 4. Conduct exploratory studies in support of Projects. As pain and stress measures are associated with reduced hippocampal volume (Project 1), we assess a range of cellular pathologies in the hippocampus with respect to subsectors of Ammon's horn. Cardiac autonomic abnormalities leading to heart rate variability are linked to risk for cognitive impairment and correlate with white matter hyperintensities (Project 2). The NP Core assesses of cerebrovascular pathology and measures of microvascular and white matter pathology to explore possible pathologic relationships to cardiovascular and autonomic measures. Aim 5. Sharing of tissue. The Neuropathology Core banks fixed and frozen brain tissue, as well as paraffin blocks on all cases. DNA and RNA are extracted from tissue, and they are also banked. Fixed and frozen tissue, as well as DNA, slides and paraffin blocks are available for sharing with qualified investigators with approval of the Administrative Core.