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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
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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.
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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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