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.
authors.affiliation: ASU-Banner Neurodegenerative Disease Research Center, Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, AZ, USA; L.J. Roberts Alzheimer's Disease Center, Banner Sun Health Research Institute, Sun City, AZ, USA; Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNS), Faculty of Health, Medicine and Life Sciences, European Graduate School of Neuroscience (EURON), Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Diego
authors.initials: D
authors.lastname: Mastroeni
authors.affiliation: ASU-Banner Neurodegenerative Disease Research Center, Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, AZ, USA; L.J. Roberts Alzheimer's Disease Center, Banner Sun Health Research Institute, Sun City, AZ, USA.
authors.forename: Elaine
authors.initials: E
authors.lastname: Delvaux
authors.affiliation: ASU-Banner Neurodegenerative Disease Research Center, Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, AZ, USA; L.J. Roberts Alzheimer's Disease Center, Banner Sun Health Research Institute, Sun City, AZ, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Nolz
authors.affiliation: Department of Neurology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yuyan
authors.initials: Y
authors.lastname: Tan
authors.affiliation: L.J. Roberts Alzheimer's Disease Center, Banner Sun Health Research Institute, Sun City, AZ, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Grover
authors.affiliation: Oddo Laboratory-Neurobiology of Aging and Dementia, Banner Sun Health Research Institute, Sun City, AZ, USA; Department of Basic Medical Sciences, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, USA.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Oddo
authors.affiliation: ASU-Banner Neurodegenerative Disease Research Center, Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, AZ, USA; L.J. Roberts Alzheimer's Disease Center, Banner Sun Health Research Institute, Sun City, AZ, USA. Electronic address: paul.coleman@bannerhealth.com.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Coleman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism*; D044127:Epigenesis, Genetic / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006657:Histones / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000378:metabolism; D008297:Male; D008745:Methylation; D008875:Middle Aged; D014158:Transcription, Genetic / Q000235:genetics; D015533:Transcriptional Activation
chemical_list: D006657:Histones; D008239:Lysine
keywords: Alzheimer's disease; Epigenetics; H3k4me3; Localization