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

Author:

Hernández Hernán Guillermo12,Sandoval-Hernández Adrián Gabriel34,Garrido-Gil Pablo56,Labandeira-Garcia José Luis56,Zelaya María Victoria7,Bayon Gustavo F8,Fernández Agustín F9,Fraga Mario F10,Arboleda Gonzalo34,Arboleda Humberto3

Affiliation:

1. PhD Program in Dentistry, Universidad Santo Tomás, Bucaramanga, Colombia

2. Research Unity, Universidad Manuela Beltrán, Bucaramanga, Colombia

3. Grupo de Neurociencias y muerte Celular, Facultad de Medicina e instituto de Genética, Universidad Nacional de Colombia, Colombia

4. Área de Bioquímica, Departamento de Química Universidad Nacional de Colombia, Colombia

5. Laboratory of Neuroanatomy and Experimental Neurology, Department of Morphological Sciences, CIMUS, Faculty of Medicine, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain

6. Networking Research Center on Neurodegenerative Diseases (CIBERNED), Madrid, Spain

7. Navarrabiomed Brain Bank, Navarra Institute for Health Research, Pamplona, Navarra, Spain

8. Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Hospital Universitario Central de Asturias (HUCA), Universidad de Oviedo, Principado de Asturias, Spain

9. Fundación para la Investigación Biosanitaria de Asturias (FINBA), Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Principado de Asturias, Spain

10. Nanomaterials and Nanotechnology Research Center (CINN-CSIC), Universidad de Oviedo, Principado de Asturias, Spain

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.

Publisher

Future Medicine Ltd

Subject

Cancer Research,Genetics

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