Neuropathology Core

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PROJECT SUMMARY (APOE U19 Core C: Neuropathology Core) The Neuropathology Core (Core C) supports the ultimate goal of understanding the ApoE Cascade Hypothesis by providing neuropathologic support to the projects and cores of the U19. A major focus of Core C efforts is on assessing the impact of APOE genotype on comorbid pathologies in Alzheimer’s disease and other aging- related conditions. The brain bank at Mayo Clinic in Jacksonville (MCJ) will be the major source of postmortem brain samples used in the cores and projects, supplemented by samples from the brain bank at Washington University in St. Louis (WUSTL). Brain samples will be crucial to analyses of biochemical and biophysical properties of brain apoE-lipoprotein particles performed by Core B and for the proteomic and transcriptomic studies performed by Core F. Core C will characterize tissues provided to the investigators in the U19 using immunoassays that measure levels of apoE, Aβ, tau, synaptic markers, glial activation markers, inflammatory cytokines, as well as markers of vascular integrity, and other aging and AD-related molecules. The role of comorbid or mixed pathology will be assessed in AD and control brains by assessing quantitative measures of amyloid deposits, amyloid angiopathy, neuronal and glial tau pathologies, α-synuclein pathology and TDP-43 pathology. Core C will work closely with Project 5 investigators to investigate neuropathologic phenotypes associated with novel genetic modifiers of APOE risk, and it will develop novel assays, as needed, to study the gene products implicated in Project 5 genetic association studies. It will assist Project 2 investigators in histologic and neuropathologic assessment of astrocytic and microglial response to Aβ-induced local damage, Aβ-induced tau spreading, and tau-mediated neurodegeneration in animal models. Finally, Core C will assist investigators in Projects 3 and 4 with digital pathologic method to systematically assess markers of glial activation and other neuropathologic measures in animal and cellular models. Core C supports individual components of the U19 by providing neuropathology services and resources to address gaps in knowledge with the ultimate goal of testing the ApoE Cascade Hypothesis. Core C will use cutting edge methods, such as digital pathology and confocal microscopy, to address critical knowledge gaps in our collective efforts to understand why APOE genotype has a profound effect on risk for AD and other ageing-related conditions. In addition, Core C will share valuable resources (brain tissues and relevant data) with the Multi-Omics, Bioinformatics, Biostatistics, and Data Management Core (Cores F and G), as well as the general scientific community via U19 web portal (www.EPAAD.org).