title: A genome-wide profiling of brain DNA hydroxymethylation in Alzheimer's disease.
abstract: BACKGROUND
  DNA methylation is a key epigenetic mechanism in brain aging and Alzheimer's disease (AD). The newly discovered 5-hydroxymethylcytosine mediates DNA demethylation, is highly abundant in the brain, and is dynamically regulated by life experiences. However, little is known about its genome-wide patterns and potential role in AD.
  
  
  METHODS
  Using a genome-wide capture followed by high-throughput sequencing, we studied the genome-wide distribution of 5-hydroxymethylcytosine at specific genomic loci in human AD brain and identified differentially hydroxymethylated regions (DhMRs) associated with AD pathology.
  
  
  RESULTS
  We identified 517 DhMRs significantly associated with neuritic plaques and 60 DhMRs associated with neurofibrillary tangles. DNA hydroxymethylation in gene bodies was predominantly positively correlated with cis-acting gene expression. Moreover, genes showing differential hydroxymethylation were significantly enriched in neurobiological processes and clustered in functional gene ontology categories.
  
  
  CONCLUSIONS
  Our results reveal a critical role of DNA hydroxymethylation in AD pathology and provide mechanistic insight into the molecular mechanisms underlying AD.
authors.affiliation: Department of Epidemiology, College of Public Health and Health Professions, University of Florida, Gainesville, FL, USA. Electronic address: jzhao5@tulane.edu.
authors.forename: Jinying
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Epidemiology, College of Public Health and Health Professions, University of Florida, Gainesville, FL, USA.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
authors.forename: Jingyun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Biostatistics and Bioinformatics, Emory University School of Public Health, Atlanta, GA, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Philip L
authors.initials: PL
authors.lastname: De Jager
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Jin
authors.affiliation: Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Bennett
mesh_terms: D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D019175:DNA Methylation; D005260:Female; D015870:Gene Expression; D056426:Genetic Loci; D006801:Humans; D008297:Male; D016874:Neurofibrillary Tangles / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D058225:Plaque, Amyloid / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000473:pathology*; D011446:Prospective Studies
keywords: Alzheimer's disease; DNA hydroxymethylation; Epigenetics; Genome-wide association; Postmortem brain