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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
2P01AG000538-34A1
Application #
8705151
Study Section
Special Emphasis Panel (ZAG1)
Project Start
Project End
Budget Start
2014-07-01
Budget End
2015-03-31
Support Year
34
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of California Irvine
Department
Type
DUNS #
City
Irvine
State
CA
Country
United States
Zip Code
92697
Spangenberg, Elizabeth E; Lee, Rafael J; Najafi, Allison R et al. (2016) Eliminating microglia in Alzheimer's mice prevents neuronal loss without modulating amyloid-β pathology. Brain 139:1265-81
Passos, Giselle F; Kilday, Kelley; Gillen, Daniel L et al. (2016) Experimental hypertension increases spontaneous intracerebral hemorrhages in a mouse model of cerebral amyloidosis. J Cereb Blood Flow Metab 36:399-404
Hatami, Asa; Monjazeb, Sanaz; Glabe, Charles (2016) The Anti-Amyloid-β Monoclonal Antibody 4G8 Recognizes a Generic Sequence-Independent Epitope Associated with α-Synuclein and Islet Amyloid Polypeptide Amyloid Fibrils. J Alzheimers Dis 50:517-25
Abbasi, Asghar; de Paula Vieira, Rodolfo; Bischof, Felix et al. (2016) Sex-specific variation in signaling pathways and gene expression patterns in human leukocytes in response to endotoxin and exercise. J Neuroinflammation 13:289
Acharya, Munjal M; Green, Kim N; Allen, Barrett D et al. (2016) Elimination of microglia improves cognitive function following cranial irradiation. Sci Rep 6:31545
Marsh, Samuel E; Abud, Edsel M; Lakatos, Anita et al. (2016) The adaptive immune system restrains Alzheimer's disease pathogenesis by modulating microglial function. Proc Natl Acad Sci U S A 113:E1316-25
Linnartz-Gerlach, Bettina; Schuy, Christine; Shahraz, Anahita et al. (2016) Sialylation of neurites inhibits complement-mediated macrophage removal in a human macrophage-neuron Co-Culture System. Glia 64:35-47
Zhang, Liang; Trushin, Sergey; Christensen, Trace A et al. (2016) Altered brain energetics induces mitochondrial fission arrest in Alzheimer's Disease. Sci Rep 6:18725
Snigdha, Shikha; Prieto, G Aleph; Petrosyan, Arpine et al. (2016) H3K9me3 Inhibition Improves Memory, Promotes Spine Formation, and Increases BDNF Levels in the Aged Hippocampus. J Neurosci 36:3611-22
Fonseca, Maria I; Chu, Shuhui; Pierce, Aimee L et al. (2016) Analysis of the Putative Role of CR1 in Alzheimer's Disease: Genetic Association, Expression and Function. PLoS One 11:e0149792

Showing the most recent 10 out of 254 publications