Abstract

Alzheimer's disease (AD) is the most common form of dementia with more than 5.5 million patients in the USA, a number that will quadruple by 2047. The disease can be characterized as an accelerated loss of cognitive functioning to such an extent that it interferes drastically with a person Aim 1. Using second generation high throughput sequencing to assess changes in chromatin modifications induced by nutritional signals and their role in the development and progression of cognitive performance and AD pathology.
Aim 2. To reveal genome-wide changes in LXR binding caused by HFD and thus to identify LXR targets whose transcriptional up- or down-regulation has a role in the development and progression of AD-like phenotype in model mice.

Public Health Relevance

This study will address questions that are important for continuing research in a field highly relevant to human health - Alzheimer's disease and changes in chromatin modifications induced by nutritional signals and their role in the development and progression of this disease. The result from this study will help us to understand the interplay between important genes and proteins involved in cholesterol transport in brain, and how the knowledge about disturbed function of those proteins can help in developing new therapeutic strategies for slowing AD progression.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG037919-03
Application #
8721296
Study Section
Molecular Neurogenetics Study Section (MNG)
Program Officer
Petanceska, Suzana
Project Start
2012-09-01
Project End
2017-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
3
Fiscal Year
2014
Total Cost
$475,000
Indirect Cost
$133,470

  Institution

Name
University of Pittsburgh
Department
Public Health & Prev Medicine
Type
Other Domestic Higher Education
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213

  Publications

Castranio, Emilie L; Wolfe, Cody M; Nam, Kyong Nyon et al. (2018) ABCA1 haplodeficiency affects the brain transcriptome following traumatic brain injury in mice expressing human APOE isoforms. Acta Neuropathol Commun 6:69
Nam, Kyong Nyon; Wolfe, Cody M; Fitz, Nicholas F et al. (2018) Integrated approach reveals diet, APOE genotype and sex affect immune response in APP mice. Biochim Biophys Acta Mol Basis Dis 1864:152-161
Nam, Kyong Nyon; Mounier, Anais; Wolfe, Cody M et al. (2017) Effect of high fat diet on phenotype, brain transcriptome and lipidome in Alzheimer's model mice. Sci Rep 7:4307
Castranio, Emilie L; Mounier, Anais; Wolfe, Cody M et al. (2017) Gene co-expression networks identify Trem2 and Tyrobp as major hubs in human APOE expressing mice following traumatic brain injury. Neurobiol Dis 105:1-14
Fitz, Nicholas F; Carter, Alexis Y; Tapias, Victor et al. (2017) ABCA1 Deficiency Affects Basal Cognitive Deficits and Dendritic Density in Mice. J Alzheimers Dis 56:1075-1085
Carter, Alexis Y; Letronne, Florent; Fitz, Nicholas F et al. (2017) Liver X receptor agonist treatment significantly affects phenotype and transcriptome of APOE3 and APOE4 Abca1 haplo-deficient mice. PLoS One 12:e0172161
Nam, Kyong Nyon; Mounier, Anais; Fitz, Nicholas F et al. (2016) RXR controlled regulatory networks identified in mouse brain counteract deleterious effects of A? oligomers. Sci Rep 6:24048
Fitz, Nicholas F; Tapias, Victor; Cronican, Andrea A et al. (2015) Opposing effects of Apoe/Apoa1 double deletion on amyloid-? pathology and cognitive performance in APP mice. Brain 138:3699-715
Lefterov, Iliya; Schug, Jonathan; Mounier, Anais et al. (2015) RNA-sequencing reveals transcriptional up-regulation of Trem2 in response to bexarotene treatment. Neurobiol Dis 82:132-140
Mounier, Anais; Georgiev, Danko; Nam, Kyong Nyon et al. (2015) Bexarotene-Activated Retinoid X Receptors Regulate Neuronal Differentiation and Dendritic Complexity. J Neurosci 35:11862-76

Showing the most recent 10 out of 17 publications