Biospecimen/Neuropathology Core

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PROJECT SUMMARY (Biospecimen / Neuropathology): Cognitive SuperAgers are 80+ year-olds with episodic memory performance that is at least as good as what would be considered normal for 50-60-year-olds. Given the normally occurring age-related loss of memory capacity, SuperAgers provide a unique resource for investigating the biological factors that promote resistance and resilience to the involutional effects of age on cognition. The Northwestern SuperAging Program has made considerable progress in addressing this question. In the course of investigations, a number of biologic, anatomic, pathologic, and molecular features have been identified in SuperAgers, which distinguish them from their peers with average cognition (Controls), including greater volume of anterior cingulate cortex (ACC), greater density of Von Economo neurons in the anterior cingulate cortex, fewer cortical plaques and tangles that are characteristic of age-related Alzheimer pathology, integrity of cortical cholinergic innervation and inheritance of different polymorphisms of the MAP2K3 gene. The goal of the proposed Consortium is to increase the subject pool of SuperAgers and Controls and to achieve a much higher representation of African American participants. The Biospecimen / Neuropathology Core of the SuperAging Consortium will collect and bank brain tissue and blood products from participants, render neuropathological diagnoses, quantitate key markers of neurodegeneration, and generate genomic, transcriptomic and plasma biomarker data for collaborative intramural and extramural studies. It will also provide brain tissue, plasma and DNA for studies proposed in Project 2 of this Consortium. It will enable the confirmation of previous findings in a larger cohort, and will allow exploration of new factors that distinguish SuperAgers from Controls. The Biospecimen / Neuropathology Core will pursue three specific aims: Aim 1. Bank blood / blood products and DNA from all participants, and postmortem brain tissue from participants that come to autopsy. Blood products, and fixed and frozen brain tissue will be banked, neuropathological diagnoses will be rendered and data from exome-wide analysis of DNA, transcriptome analysis of cortical tissue, and plasma biomarkers will be generated and archived. Aim 2. Confirm previous biologic, anatomic, pathologic and genetic findings in a significantly larger cohort of SuperAgers and Controls obtained through this Consortium. Existing observations on the SuperAging phenotype, which were generated in small cohorts, will be confirmed in a larger pool of participants. Aim 3. Explore new factors that may distinguish SuperAgers from Controls in a large cohort, including measures of neuronal and synaptic integrity. The assembled team of investigators has extensive expertise and record of productivity relevant to achieving the goals of this core. The activities of the Biospecimen / Neuropathology Core will facilitate investigation of factors that may contribute to the SuperAging phenotype and will help identify potential targets for interventions that will allow normal elderly to preserve cognitive function and combat dementia.