Alzheimer’s Disease DNA Methylome of Pyramidal Layers in Frontal Cortex: Laser-Assisted Microdissection Study

Abstract

Objective: To study DNA methylation patterns of cortical pyramidal layers susceptible to late-onset Alzheimer’s disease (LOAD) neurodegeneration. Methods: 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. Results: 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. Conclusion: 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.

Keywords::

• Alzheimer’s disease
• DNA methylation
• epigenetics
• epigenomics
• methylomics

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: https://www.tandfonline.com/doi/suppl/10.2217/epi-2017-0160

Acknowledgements

The authors acknowledge T Peters for his guidance in personal communications related to DMRcate built in-house code.

Disclosure

H Guillermo Hernández performed part of this work as part of the PhD thesis in the Universidad Nacional de Colombia, Bogotá, Colombia.

Financial & competing interests disclosure

This study was funded by Colciencias (numbers: 110161538259/498-2012). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This study was funded by Colciencias (numbers: 110161538259/498-2012). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.