The goal of this proposal is to obtain, at autopsy, brain tissue from individuals who have been clinically well-characterized during life and to prepare and maintain the tissue in a manner that is optimal for the research studies. Brain tissue will be obtained from individuals who are neurologically normal, or diagnosed as """"""""probable"""""""" Alzheimer's disease (AD), possible AD, and non-AD dementia (Pick's disease, Multi-infarct Dementia, etc.). All of the individuals for whom we have consents will have been evaluated thoroughly at the UCI AD clinic. This includes a group of control individuals who are participants in a Foster Grandparent Program and who have been evaluated for the past four years in a study examining physical and mental indices of age-related decline. The autopsy protocol is designed to provide fresh frozen tissue for biochemical and molecular studies and fixed tissue for neuropathological evaluation and for immunochemistry and in situ hybridization One hemisphere of the brain is dissected, with the various regions snap-frozen and stored at -70oC. Regions can also be placed into fixative, depending on the specific needs of the research studies. The frozen sections include the entire rostral-caudal extent of the hippocampus. The opposite hemisphere is sliced into 7 mm coronal sections, with alternating sections fixed in 4% paraformaldehyde or frozen between prechilled (-40oC) aluminum plates. Areas for neuropathological evaluation are removed from the fixed sections and are paraffin-embedded. The remaining tissues are equilibrated in 18% sucrose in phosphate-buffered saline (RNase free), frozen, and stored at - 70oC. This tissue is used for immunochemical and in situ hybridization studies. The Human Brain Tissue Repository will also provide neuropathological assessment on tissues adjacent to those used for biochemical studies.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
2P01AG000538-14
Application #
3808913
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
14
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of California Irvine
Department
Type
DUNS #
161202122
City
Irvine
State
CA
Country
United States
Zip Code
92697
Sosna, Justyna; Philipp, Stephan; Albay 3rd, Ricardo et al. (2018) Early long-term administration of the CSF1R inhibitor PLX3397 ablates microglia and reduces accumulation of intraneuronal amyloid, neuritic plaque deposition and pre-fibrillar oligomers in 5XFAD mouse model of Alzheimer's disease. Mol Neurodegener 13:11
Tong, Liqi; Prieto, G Aleph; Cotman, Carl W (2018) IL-1? suppresses cLTP-induced surface expression of GluA1 and actin polymerization via ceramide-mediated Src activation. J Neuroinflammation 15:127
Hainsworth, A H; Lee, S; Foot, P et al. (2018) Super-resolution imaging of subcortical white matter using stochastic optical reconstruction microscopy (STORM) and super-resolution optical fluctuation imaging (SOFI). Neuropathol Appl Neurobiol 44:417-426
Krotee, Pascal; Griner, Sarah L; Sawaya, Michael R et al. (2018) Common fibrillar spines of amyloid-? and human islet amyloid polypeptide revealed by microelectron diffraction and structure-based inhibitors. J Biol Chem 293:2888-2902
Prieto, G Aleph; Tong, Liqi; Smith, Erica D et al. (2018) TNF? and IL-1? but not IL-18 Suppresses Hippocampal Long-Term Potentiation Directly at the Synapse. Neurochem Res :
Carlos, Anthony J; Tong, Liqi; Prieto, G Aleph et al. (2017) IL-1? impairs retrograde flow of BDNF signaling by attenuating endosome trafficking. J Neuroinflammation 14:29
Fonseca, Maria I; Chu, Shu-Hui; Hernandez, Michael X et al. (2017) Cell-specific deletion of C1qa identifies microglia as the dominant source of C1q in mouse brain. J Neuroinflammation 14:48
Abud, Edsel M; Ramirez, Ricardo N; Martinez, Eric S et al. (2017) iPSC-Derived Human Microglia-like Cells to Study Neurological Diseases. Neuron 94:278-293.e9
Jun, Gyungah R; Chung, Jaeyoon; Mez, Jesse et al. (2017) Transethnic genome-wide scan identifies novel Alzheimer's disease loci. Alzheimers Dement 13:727-738
Gonzalez, Bianca; Abud, Edsel M; Abud, Abigail M et al. (2017) Tau Spread, Apolipoprotein E, Inflammation, and More: Rapidly Evolving Basic Science in Alzheimer Disease. Neurol Clin 35:175-190

Showing the most recent 10 out of 281 publications