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Whole transcriptome profiling of Late-Onset Alzheimer’s Disease patients provides insights into the molecular changes involved in the disease
Alzheimer’s Disease (AD) is the most common cause of dementia affecting the elderly population worldwide. We have performed a comprehensive transcriptome profiling of Late-Onset AD (LOAD) patients using second generation sequencing technologies, identifying 2,064 genes, 47 lncRNAs and 4 miRNAs whose...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5844946/ https://www.ncbi.nlm.nih.gov/pubmed/29523845 http://dx.doi.org/10.1038/s41598-018-22701-2 |
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author | Annese, Anita Manzari, Caterina Lionetti, Claudia Picardi, Ernesto Horner, David S. Chiara, Matteo Caratozzolo, Mariano Francesco Tullo, Apollonia Fosso, Bruno Pesole, Graziano D’Erchia, Anna Maria |
author_facet | Annese, Anita Manzari, Caterina Lionetti, Claudia Picardi, Ernesto Horner, David S. Chiara, Matteo Caratozzolo, Mariano Francesco Tullo, Apollonia Fosso, Bruno Pesole, Graziano D’Erchia, Anna Maria |
author_sort | Annese, Anita |
collection | PubMed |
description | Alzheimer’s Disease (AD) is the most common cause of dementia affecting the elderly population worldwide. We have performed a comprehensive transcriptome profiling of Late-Onset AD (LOAD) patients using second generation sequencing technologies, identifying 2,064 genes, 47 lncRNAs and 4 miRNAs whose expression is specifically deregulated in the hippocampal region of LOAD patients. Moreover, analyzing the hippocampal, temporal and frontal regions from the same LOAD patients, we identify specific sets of deregulated miRNAs for each region, and we confirm that the miR-132/212 cluster is deregulated in each of these regions in LOAD patients, consistent with these miRNAs playing a role in AD pathogenesis. Notably, a luciferase assay indicates that miR-184 is able to target the 3’UTR NR4A2 - which is known to be involved in cognitive functions and long-term memory and whose expression levels are inversely correlated with those of miR-184 in the hippocampus. Finally, RNA editing analysis reveals a general RNA editing decrease in LOAD hippocampus, with 14 recoding sites significantly and differentially edited in 11 genes. Our data underline specific transcriptional changes in LOAD brain and provide an important source of information for understanding the molecular changes characterizing LOAD progression. |
format | Online Article Text |
id | pubmed-5844946 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-58449462018-03-14 Whole transcriptome profiling of Late-Onset Alzheimer’s Disease patients provides insights into the molecular changes involved in the disease Annese, Anita Manzari, Caterina Lionetti, Claudia Picardi, Ernesto Horner, David S. Chiara, Matteo Caratozzolo, Mariano Francesco Tullo, Apollonia Fosso, Bruno Pesole, Graziano D’Erchia, Anna Maria Sci Rep Article Alzheimer’s Disease (AD) is the most common cause of dementia affecting the elderly population worldwide. We have performed a comprehensive transcriptome profiling of Late-Onset AD (LOAD) patients using second generation sequencing technologies, identifying 2,064 genes, 47 lncRNAs and 4 miRNAs whose expression is specifically deregulated in the hippocampal region of LOAD patients. Moreover, analyzing the hippocampal, temporal and frontal regions from the same LOAD patients, we identify specific sets of deregulated miRNAs for each region, and we confirm that the miR-132/212 cluster is deregulated in each of these regions in LOAD patients, consistent with these miRNAs playing a role in AD pathogenesis. Notably, a luciferase assay indicates that miR-184 is able to target the 3’UTR NR4A2 - which is known to be involved in cognitive functions and long-term memory and whose expression levels are inversely correlated with those of miR-184 in the hippocampus. Finally, RNA editing analysis reveals a general RNA editing decrease in LOAD hippocampus, with 14 recoding sites significantly and differentially edited in 11 genes. Our data underline specific transcriptional changes in LOAD brain and provide an important source of information for understanding the molecular changes characterizing LOAD progression. Nature Publishing Group UK 2018-03-09 /pmc/articles/PMC5844946/ /pubmed/29523845 http://dx.doi.org/10.1038/s41598-018-22701-2 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Annese, Anita Manzari, Caterina Lionetti, Claudia Picardi, Ernesto Horner, David S. Chiara, Matteo Caratozzolo, Mariano Francesco Tullo, Apollonia Fosso, Bruno Pesole, Graziano D’Erchia, Anna Maria Whole transcriptome profiling of Late-Onset Alzheimer’s Disease patients provides insights into the molecular changes involved in the disease |
title | Whole transcriptome profiling of Late-Onset Alzheimer’s Disease patients provides insights into the molecular changes involved in the disease |
title_full | Whole transcriptome profiling of Late-Onset Alzheimer’s Disease patients provides insights into the molecular changes involved in the disease |
title_fullStr | Whole transcriptome profiling of Late-Onset Alzheimer’s Disease patients provides insights into the molecular changes involved in the disease |
title_full_unstemmed | Whole transcriptome profiling of Late-Onset Alzheimer’s Disease patients provides insights into the molecular changes involved in the disease |
title_short | Whole transcriptome profiling of Late-Onset Alzheimer’s Disease patients provides insights into the molecular changes involved in the disease |
title_sort | whole transcriptome profiling of late-onset alzheimer’s disease patients provides insights into the molecular changes involved in the disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5844946/ https://www.ncbi.nlm.nih.gov/pubmed/29523845 http://dx.doi.org/10.1038/s41598-018-22701-2 |
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