title: Epigenomics of Alzheimer's disease.
abstract: Alzheimer's disease (AD) is a large and growing public health problem. It is characterized by the accumulation of amyloid β peptides and abnormally phosphorylated tau proteins that are associated with cognitive decline and dementia. Much has been learned about the genomics of AD from linkage analyses and, more recently, genome-wide association studies. Several but not all aspects of the genomic landscape are involved in amyloid β metabolism. The moderate concordance of disease among twins suggests other factors, potentially epigenomic factors, are related to AD. We are at the earliest stages of examining the relation of the epigenome to the clinical and pathologic phenotypes that characterize AD. Our literature review suggests that there is some evidence of age-related changes in human brain methylation. Unfortunately, studies of AD have been relatively small with limited coverage of methylation sites and microRNA, let alone other epigenomic marks. We are in the midst of 2 large studies of human brains including coverage of more than 420,000 autosomal cytosine-guanine dinucleotides with the Illumina Infinium HumanMethylation450 BeadArray, and histone acetylation with chromatin immunoprecipitation sequencing. We present descriptive data to help inform other researchers what to expect from these approaches to better design and power their studies. We then discuss future directions to inform on the epigenomic architecture of AD.
authors.affiliation: Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Ill. Electronic address: David_A_Bennett@Rush.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: Bennett
authors.affiliation: Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Ill.
authors.forename: Lei
authors.initials: L
authors.lastname: Yu
authors.affiliation: Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Ill.
authors.forename: Jingyun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry, Brigham and Women's Hospital, Boston, Mass; Harvard Medical School, Boston, Mass; Program in Medical and Population Genetics, Broad Institute, Cambridge, Mass.
authors.forename: Gyan P
authors.initials: GP
authors.lastname: Srivastava
authors.affiliation: Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry, Brigham and Women's Hospital, Boston, Mass; Harvard Medical School, Boston, Mass; Program in Medical and Population Genetics, Broad Institute, Cambridge, Mass.
authors.forename: Cristin
authors.initials: C
authors.lastname: Aubin
authors.affiliation: Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry, Brigham and Women's Hospital, Boston, Mass; Harvard Medical School, Boston, Mass; Program in Medical and Population Genetics, Broad Institute, Cambridge, Mass.
authors.forename: Philip L
authors.initials: PL
authors.lastname: De Jager
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D053327:Apolipoprotein E4 / Q000235:genetics; D001921:Brain / Q000378:metabolism / Q000473:pathology; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D055106:Genome-Wide Association Study; D006657:Histones / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D057170:Translational Research, Biomedical
chemical_list: D053327:Apolipoprotein E4; D006657:Histones; D035683:MicroRNAs