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Epigenomics ; 10(11): 1365-1382, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30324800

RESUMO

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.


Assuntos
Doença de Alzheimer/genética , Metilação de DNA , Lobo Frontal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Idoso , Idoso de 80 Anos ou mais , Proteínas de Ligação a DNA/genética , Feminino , Glutationa S-Transferase pi/genética , Proteínas de Homeodomínio/genética , Humanos , Microdissecção e Captura a Laser , Masculino , Proteínas Nucleares/genética , Estresse Oxidativo , Células Piramidais/metabolismo , Transmissão Sináptica , Transativadores , Proteínas Supressoras de Tumor/genética
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