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. A, 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 A assays to individual investigators. All program investigators require either A peptides, preparations of different types of A assembly states, or both soluble and insoluble A 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

Public Health Relevance

Alzheimer disease is a devastating neurodegenerative disorder that impairs memory and causes cognitive and psychiatric deficits. The collaborative effort of this program project, which capitalizes on the unique strengths of each investigator and with support from this Core, will improve the scientific knowledge of AD; contribute to a better understanding of infiammation and AD, which will translate to new potential therapies.

National Institute of Health (NIH)
Research Program Projects (P01)
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Special Emphasis Panel (ZAG1)
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University of California Irvine
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Rice, Rachel A; Berchtold, Nicole C; Cotman, Carl W et al. (2014) Age-related downregulation of the CaV3.1 T-type calcium channel as a mediator of amyloid beta production. Neurobiol Aging 35:1002-11
Elmore, Monica R P; Najafi, Allison R; Koike, Maya A et al. (2014) Colony-stimulating factor 1 receptor signaling is necessary for microglia viability, unmasking a microglia progenitor cell in the adult brain. Neuron 82:380-97
Berchtold, Nicole C; Sabbagh, Marwan N; Beach, Thomas G et al. (2014) Brain gene expression patterns differentiate mild cognitive impairment from normal aged and Alzheimer's disease. Neurobiol Aging 35:1961-72
Hatami, Asa; Albay 3rd, Ricardo; Monjazeb, Sanaz et al. (2014) Monoclonal antibodies against A?42 fibrils distinguish multiple aggregation state polymorphisms in vitro and in Alzheimer disease brain. J Biol Chem 289:32131-43
Smith, Erica D; Prieto, G Aleph; Tong, Liqi et al. (2014) Rapamycin and interleukin-1? impair brain-derived neurotrophic factor-dependent neuron survival by modulating autophagy. J Biol Chem 289:20615-29
Pensalfini, Anna; Albay 3rd, Ricardo; Rasool, Suhail et al. (2014) Intracellular amyloid and the neuronal origin of Alzheimer neuritic plaques. Neurobiol Dis 71:53-61
Passos, Giselle F; Medeiros, Rodrigo; Cheng, David et al. (2013) The bradykinin B1 receptor regulates A? deposition and neuroinflammation in Tg-SwDI mice. Am J Pathol 182:1740-9
Medeiros, Rodrigo; LaFerla, Frank M (2013) Astrocytes: conductors of the Alzheimer disease neuroinflammatory symphony. Exp Neurol 239:133-8
Benoit, Marie E; Hernandez, Michael X; Dinh, Minhan L et al. (2013) C1q-induced LRP1B and GPR6 proteins expressed early in Alzheimer disease mouse models, are essential for the C1q-mediated protection against amyloid-* neurotoxicity. J Biol Chem 288:654-65
Fonseca, Maria I; McGuire, Susan O; Counts, Scott E et al. (2013) Complement activation fragment C5a receptors, CD88 and C5L2, are associated with neurofibrillary pathology. J Neuroinflammation 10:25

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