Early epigenetic changes of Alzheimer's disease in the human hippocampus
| Autor: | María Victoria Zelaya, Miren Roldán, Amaya Urdánoz-Casado, Janire Vicuña-Urriza, Alberto Labarga, Blanca Acha, Idoia Blanco-Luquin, Maite Mendioroz, Javier Sánchez-Ruiz de Gordoa, Iván Méndez-López, Carolina Cabello |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research Fatty Acid Elongases Hippocampus tau Proteins Disease Biology Bioinformatics Epigenesis Genetic Histones 03 medical and health sciences 0302 clinical medicine Alzheimer Disease Humans Epigenetics Molecular Biology Epigenetic biomarkers DNA Methylation 030104 developmental biology Histone 030220 oncology & carcinogenesis DNA methylation biology.protein Aspartate Aminotransferase Cytoplasmic Research Paper |
| Zdroj: | Epigenetics |
| ISSN: | 1559-2308 |
| Popis: | The discovery of new biomarkers would be very valuable to improve the detection of early Alzheimer’s disease (AD). DNA methylation marks may serve as epigenetic biomarkers of early AD. Here we identified epigenetic marks that are present in the human hippocampus from the earliest stages of AD. A previous methylome dataset of the human AD hippocampus was used to select a set of eight differentially methylated positions (DMPs) since early AD stages. Next, bisulphite pyrosequencing was performed in an expanded homogeneous cohort of 18 pure controls and 35 hippocampal samples with neuropathological changes of pure AD. Correlation between DNA methylation levels in DMPs and phospho-tau protein burden assessed by immunohistochemistry in the hippocampus was also determined. We found four DMPs showing higher levels of DNA methylation at early AD stages compared to controls, involving ELOVL2, GIT1/TP53I13 and the histone gene locus at chromosome 6. DNA methylation levels assessed by bisulphite pyrosequencing correlated with phospho-tau protein burden for ELOVL2 and HIST1H3E/HIST1H3 F genes. In this discovery study, a set of four epigenetic marks of early AD stages have been identified in the human hippocampus. It would be worth studying in-depth the specific pathways related to these epigenetic marks. These early alterations in DNA methylation in the AD hippocampus could be regarded as candidate biomarkers to be explored in future translational studies. AD: Alzheimer’s disease; DMPs: Differentially methylated positions; CSF: Cerebrospinal fluid; βA42: β-amyloid 42; PET: positron emission tomography; 5mC: 5-methyl cytosine; CpG: cytosine-guanine dinucleotides; ANK1: ankyrin-1; BIN1: amphiphysin II; p-tau: hyperphosphorylated tau; CERAD: Consortium to Establish A Registry for Alzheimer’s Disease; SD: standard deviation; ANOVA: one-way analysis of variance; VLCFAs: very long-chain fatty acids; DHA: docosahexaenoic acid; mTOR: mechanistic target of rapamycin. |
| Databáze: | OpenAIRE |
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