@article{4072588ea1b34e3688d4d323e06c66fb,
title = "Aberrant intracellular localization of H3k4me3 demonstrates an early epigenetic phenomenon in Alzheimer's disease",
abstract = "We have previously reported in Alzheimer's disease (AD) the mislocalization of epigenetic molecules between the cell nucleus and the cytoplasm. We have extended our finding to include the aberrant localization of histone 3 trimethylation on lysine 4 (H3k4me3), an epigenetic mark associated with actively transcribing genes as well as those poised for transcription. These findings raise the question of where the ectopic localization of H3k4me3 fits within the cascade of cell biological events in the progression of AD. We, therefore, examined the expression and intracellular location of H3k4me3 as a function of Braak stage and also in relation to a series of tau markers that are indicative of disease state. Both lines of evidence showed that ectopic localization of H3k4me3 is early in the course of disease. Because of the known role of H3k4me3 in the expression of synaptic genes, our data suggest an epigenetic role in synaptic deficits early in the course of AD.",
keywords = "Alzheimer's disease, Epigenetics, H3k4me3, Localization",
author = "Diego Mastroeni and Elaine Delvaux and Jennifer Nolz and Yuyan Tan and Andrew Grover and Salvatore Oddo and Coleman, {Paul D.}",
note = "Funding Information: The authors are grateful to the Banner Sun Health Research Institute Brain and Body Donation Program of Sun City, Arizona for the provision of human brain samples. The Brain and Body Donation Program is supported by the National Institute of Neurological Disorders and Stroke (U24 NS072026 National Brain and Tissue Resource for Parkinson's Disease and Related Disorders), the National Institute on Aging (P30 AG19610 Arizona Alzheimer's Disease Core Center), the Arizona Department of Health Services (contract 211002, Arizona Alzheimer's Research Center), the Arizona Biomedical Research Commission (contracts 4001, 0011, 05-901, and 1001 to the Arizona Parkinson's Disease Consortium), and the Michael J. Fox Foundation for Parkinson's Research. This work was supported by NIH R01 AG036400 and AARC DHS Award FY 2012 to Paul D. Coleman; NIRG-14-321390 and ADHS14-080000 FY 2015 to Diego Mastroeni; and NIH R01 AG037637 to Salvatore Oddo. Diego Mastroeni discovered the finding, wrote the article, and contributed to the immunohistochemistry and statistical analysis; Elaine Delvaux contributed to the experimental design and statistics; Jennifer Nolz contributed to the immunohistochemistry on human and mice, cell counting and/or quantification; Yuyan Tan contributed to the immunohistochemistry and data analysis; Andrew Grover contributed to the manuscript preparation and data analysis; Salvatore Oddo contributed to the manuscript preparation and mice preparation for immunohistochemistry; Paul D. Coleman contributed to the manuscript preparation, experimental design and statistics. Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",
year = "2015",
month = dec,
doi = "10.1016/j.neurobiolaging.2015.08.017",
language = "English (US)",
volume = "36",
pages = "3121--3129",
journal = "Neurobiology of Aging",
issn = "0197-4580",
publisher = "Elsevier Inc.",
number = "12",
}