This core provides specialized services, required by at least three of the four projects ofthe PPG. These services are best coordinated by a core to increase efficiencies of time and cost, promote scientific synergies, and maximally utilize dedicated highly specialized facilities. This PPG is a multidisciplinary investigation of in vivo and in vitro models of endosomal, autophagic, and lysosomal abnormalities in Alzheimer's disease (AD) considered critical to AD pathogenesis. Core C acquires or generates critical reagents, eg. antibodies and cell lines, that are used in every project and must be maintained under rigorously controlled conditions to allow reliable comparisons of information across projects.
The specific aims are: 1. To acquire, store and efficiently distribute well-characterized tissues (brains and fibroblasts) from cases of AD, FAD, Trisomy 21 and non-demented and non-AD neurological controls in a coordinated manner for studies in the PPG. Cultured primary mouse neurons prepared under standardized conditions will be distributed routinely. 2. To perform electron microscopy and immunogold electron microscopy on cell and mouse models and human brains. 3. To perform ELISA measurements of Abeta 40 and Abeta 42 to quantify endogenous murine Abeta and human Abeta in AD brains, brains of mouse models and media and lysates of fibroblasts and other cell models. 4. To provide specialized histological procedures, fluorescence/confocal applications, morphometric techniques and neurosurgical procedures as needed for all four projects as well as provide training on laser confocal microscopy and video-fluorescent microscopy. 5. To maintain and distribute polyclonal and monoclonal antibodies and generate additional anfibodies. 6. To administer to mouse models behavioral assays of memory and motor performances from a highly standardized battery of validated tests. The Core serves all projects and is essential to their success.

Public Health Relevance

This Core provides well-characterized biological materials and standardized state-of-the-art technical services needed to perform the studies in this PPG, which aims to understand how AD develops and will identify new directions for the therapy of AD and possibly other aging-related neurodegenerative diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG017617-13
Application #
8572256
Study Section
Special Emphasis Panel (ZAG1-ZIJ-6)
Project Start
Project End
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
13
Fiscal Year
2013
Total Cost
$309,381
Indirect Cost
$117,529
Name
Nathan Kline Institute for Psychiatric Research
Department
Type
DUNS #
167204762
City
Orangeburg
State
NY
Country
United States
Zip Code
10962
Alldred, Melissa J; Lee, Sang Han; Petkova, Eva et al. (2015) Expression profile analysis of vulnerable CA1 pyramidal neurons in young-Middle-Aged Ts65Dn mice. J Comp Neurol 523:61-74
Alldred, Melissa J; Lee, Sang Han; Petkova, Eva et al. (2015) Expression profile analysis of hippocampal CA1 pyramidal neurons in aged Ts65Dn mice, a model of Down syndrome (DS) and Alzheimer's disease (AD). Brain Struct Funct 220:2983-96
Kelley, Christy M; Powers, Brian E; Velazquez, Ramon et al. (2014) Sex differences in the cholinergic basal forebrain in the Ts65Dn mouse model of Down syndrome and Alzheimer's disease. Brain Pathol 24:33-44
Counts, Scott E; Alldred, Melissa J; Che, Shaoli et al. (2014) Synaptic gene dysregulation within hippocampal CA1 pyramidal neurons in mild cognitive impairment. Neuropharmacology 79:172-9
Yan, Jian; Ginsberg, Stephen D; Powers, Brian et al. (2014) Maternal choline supplementation programs greater activity of the phosphatidylethanolamine N-methyltransferase (PEMT) pathway in adult Ts65Dn trisomic mice. FASEB J 28:4312-23
Xue, Xue; Wang, Li-Rong; Sato, Yutaka et al. (2014) Single-walled carbon nanotubes alleviate autophagic/lysosomal defects in primary glia from a mouse model of Alzheimer's disease. Nano Lett 14:5110-7
Kaur, Gurjinder; Sharma, Ajay; Xu, Wenjin et al. (2014) Glutamatergic transmission aberration: a major cause of behavioral deficits in a murine model of Down's syndrome. J Neurosci 34:5099-106
Kelley, Christy M; Powers, Brian E; Velazquez, Ramon et al. (2014) Maternal choline supplementation differentially alters the basal forebrain cholinergic system of young-adult Ts65Dn and disomic mice. J Comp Neurol 522:1390-410
Wesson, Daniel W; Morales-Corraliza, Jose; Mazzella, Matthew J et al. (2013) Chronic anti-murine Aýý immunization preserves odor guided behaviors in an Alzheimer's ýý-amyloidosis model. Behav Brain Res 237:96-102
Nixon, Ralph A (2013) The role of autophagy in neurodegenerative disease. Nat Med 19:983-97

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