TISSUE, PEPTIDE AND GENETICS RESOURCE CORE

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Core B: Tissue, Peptide and Genetics Resource Core This program project is broadly focused on understanding the mechanisms by which inflammation modulates AD pathogenesis. An additional theme of this project is focused on how proteins recently identified by Genome Wide Association Studies (GWAS) in Alzheimer disease (AD) modulate the infiammatory cascade, contribute to endocytic dysfunction, and impair protein trafficking/clearance, and thereby increase AD risk. An overarching goal of the program project is to utilize molecular, cellular and animal model systems to identify and characterize mechanisms and pathways associated AD neuropathology (e.g. Aß, tau, inflammation, and synaptic and neuronal loss) and neuroinflammation. The outcome of these studies can be translated and verifled in human autopsy brain specimens. The Tissue, Peptide, and Genetics Core plays a key role in support of the program project research goals. To achieve these goals, the Tissue, Peptide and Genetics Core has four aims. (1) Produce and provide well-characterized, high quality peptides, antibodies, and Aß assays to individual investigators. All program investigators require either Aß peptides, preparations of different types of Aß assembly states, or both soluble and insoluble Aß measurements. (2) Carry out high- throughput analysis for newly identified single nucleotide polymorphism (SNP) risk alleles for late-onset AD to support investigator research. Individual investigators will require SNP data from living subjects, from induced pluripotent stem cells derived from fibroblasts, as well as from brain autopsy specimens. (3) The Tissue, Peptide, and Genetics Core will support program project research by providing dedicated high quality clinically and neuropathologically characterized human autopsy and biological specimens (blood, fibroblasts) for use by program project investigators (including SNP data from GWAS-identified AD-risk genes). (4) Coordinate and maintain a database of quantitative variables and of resource use to be shared among program investigators. The Core collates and integrates quantitative neurobiological and clinical data, which will be provided to investigators to allow the seamless integration of data from individual research projects