Alzheimer's disease DNA methylome of pyramidal layers in frontal cortex: laser-assisted microdissection study

To study DNA methylation patterns of cortical pyramidal layers susceptible to late-onset Alzheimer's disease (LOAD) neurodegeneration. Laser-assisted microdissection to select pyramidal layers' cells in frontal cortex of 32 human brains (18 LOAD) and Infinium DNA Methylation 450K analysis...

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Bibliographic Details
Published in:Epigenomics 2018-11, Vol.10 (11), p.1365-1382
Main Authors: Hernández, Hernán Guillermo, Sandoval-Hernández, Adrián Gabriel, Garrido-Gil, Pablo, Labandeira-Garcia, José Luis, Zelaya, María Victoria, Bayon, Gustavo F, Fernández, Agustín F, Fraga, Mario F, Arboleda, Gonzalo, Arboleda, Humberto
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing - genetics
Aged
Aged, 80 and over
Alzheimer Disease - genetics
Alzheimer's disease
Cortex (frontal)
Deoxyribonucleic acid
DNA
DNA Methylation
DNA-Binding Proteins - genetics
epigenetics
epigenomics
Female
Frontal Lobe - metabolism
Genes
Glutathione S-Transferase pi - genetics
Glutathione transferase
Homeodomain Proteins - genetics
Humans
Laser Capture Microdissection
Male
methylomics
Neurodegeneration
Neurodegenerative diseases
Nuclear Proteins - genetics
Oxidative Stress
Pyramidal Cells - metabolism
Synaptic Transmission
Tumor Suppressor Proteins - genetics
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Summary:To study DNA methylation patterns of cortical pyramidal layers susceptible to late-onset Alzheimer's disease (LOAD) neurodegeneration. Laser-assisted microdissection to select pyramidal layers' cells in frontal cortex of 32 human brains (18 LOAD) and Infinium DNA Methylation 450K analysis were performed to find differential methylated positions and regions, in addition to the corresponding gene set functional enrichment analyses. Differential hypermethylation in several genomic regions and genes mainly in HOXA3, GSTP1, CXXC1-3 and BIN1. The functional enrichment analysis revealed genes significantly related to oxidative-stress and synapsis. The present results indicate the differentially methylated genes related to neural projections, synapsis, oxidative stress and epigenetic regulator genes and represent the first epigenome of cortical pyramidal layers in LOAD.
ISSN:1750-1911
1750-192X
DOI:10.2217/epi-2017-0160