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.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZAG1-ZIJ-6)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Nathan Kline Institute for Psychiatric Research
United States
Zip Code
Li, Wei; Sultana, Nargis; Siraj, Nabeel et al. (2016) Autophagy dysfunction and regulatory cystatin C in macrophage death of atherosclerosis. J Cell Mol Med 20:1664-72
Mathews, Paul M; Levy, Efrat (2016) Cystatin C in aging and in Alzheimer's disease. Ageing Res Rev 32:38-50
Rosa, Elyse; Mahendram, Sujeivan; Ke, Yazi D et al. (2016) Tau downregulates BDNF expression in animal and cellular models of Alzheimer's disease. Neurobiol Aging 48:135-142
Colacurcio, Daniel J; Nixon, Ralph A (2016) Disorders of lysosomal acidification-The emerging role of v-ATPase in aging and neurodegenerative disease. Ageing Res Rev 32:75-88
Strupp, Barbara J; Powers, Brian E; Velazquez, Ramon et al. (2016) Maternal Choline Supplementation: A Potential Prenatal Treatment for Down Syndrome and Alzheimer's Disease. Curr Alzheimer Res 13:97-106
Rao, Mala V; Campbell, Jabbar; Palaniappan, Arti et al. (2016) Calpastatin inhibits motor neuron death and increases survival of hSOD1(G93A) mice. J Neurochem 137:253-65
Tiernan, Chelsea T; Ginsberg, Stephen D; Guillozet-Bongaarts, Angela L et al. (2016) Protein homeostasis gene dysregulation in pretangle-bearing nucleus basalis neurons during the progression of Alzheimer's disease. Neurobiol Aging 42:80-90
Kim, S; Sato, Y; Mohan, P S et al. (2016) Evidence that the rab5 effector APPL1 mediates APP-βCTF-induced dysfunction of endosomes in Down syndrome and Alzheimer's disease. Mol Psychiatry 21:707-16
Jiang, Ying; Rigoglioso, Andrew; Peterhoff, Corrinne M et al. (2016) Partial BACE1 reduction in a Down syndrome mouse model blocks Alzheimer-related endosomal anomalies and cholinergic neurodegeneration: role of APP-CTF. Neurobiol Aging 39:90-8
Morales-Corraliza, Jose; Wong, Harrison; Mazzella, Matthew J et al. (2016) Brain-Wide Insulin Resistance, Tau Phosphorylation Changes, and Hippocampal Neprilysin and Amyloid-β Alterations in a Monkey Model of Type 1 Diabetes. J Neurosci 36:4248-58

Showing the most recent 10 out of 141 publications