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Transl Res DOI:10.1016/j.trsl.2014.05.006

Epigenomics of Alzheimer's disease.

Publication TypeJournal Article
Year of Publication2015
AuthorsBennett, DA, Yu, L, Yang, J, Srivastava, GP, Aubin, C, De Jager, PL
JournalTransl Res
Volume165
Issue1
Pages200-20
Date Published2015 Jan
ISSN1878-1810
KeywordsAlzheimer Disease, Apolipoprotein E4, Brain, DNA Methylation, Epigenesis, Genetic, Genome-Wide Association Study, Histones, Humans, MicroRNAs, Mutation, Translational Medical Research
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.

URLhttp://linkinghub.elsevier.com/retrieve/pii/S1931-5244(14)00169-8
DOI10.1016/j.trsl.2014.05.006
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/24905038?dopt=Abstract

Alternate JournalTransl Res
PubMed ID24905038
PubMed Central IDPMC4233194
Grant ListU01 AG046152 / AG / NIA NIH HHS / United States
RF1 AG015819 / AG / NIA NIH HHS / United States
R01AG36836 / AG / NIA NIH HHS / United States
R01AG36042 / AG / NIA NIH HHS / United States
R01 AG017917 / AG / NIA NIH HHS / United States
R01AG17917 / AG / NIA NIH HHS / United States
U01AG46152 / AG / NIA NIH HHS / United States
R01 AG036042 / AG / NIA NIH HHS / United States
P30 AG010161 / AG / NIA NIH HHS / United States
RC2AG36547 / AG / NIA NIH HHS / United States
RC2 AG036547 / AG / NIA NIH HHS / United States
R01AG15819 / AG / NIA NIH HHS / United States
P30AG10161 / AG / NIA NIH HHS / United States
R01 AG036836 / AG / NIA NIH HHS / United States
R01 AG015819 / AG / NIA NIH HHS / United States