dc.contributor.author | Iatrou, A | |
dc.contributor.author | Kenis, G | |
dc.contributor.author | Rutten, BPF | |
dc.contributor.author | Lunnon, K | |
dc.contributor.author | van den Hove, DLA | |
dc.date.accessioned | 2018-10-04T10:16:44Z | |
dc.date.issued | 2016-09-14 | |
dc.description.abstract | Even though the etiology of Alzheimer's disease (AD) remains unknown, it is suggested that an interplay among genetic, epigenetic and environmental factors is involved. An increasing body of evidence pinpoints that dysregulation in the epigenetic machinery plays a role in AD. Recent developments in genomic technologies have allowed for high throughput interrogation of the epigenome, and epigenome-wide association studies have already identified unique epigenetic signatures for AD in the cortex. Considerable evidence suggests that early dysregulation in the brainstem, more specifically in the raphe nuclei and the locus coeruleus, accounts for the most incipient, non-cognitive symptomatology, indicating a potential causal relationship with the pathogenesis of AD. Here we review the advancements in epigenomic technologies and their application to the AD research field, particularly with relevance to the brainstem. In this respect, we propose the assessment of epigenetic signatures in the brainstem as the cornerstone of interrogating causality in AD. Understanding how epigenetic dysregulation in the brainstem contributes to AD susceptibility could be of pivotal importance for understanding the etiology of the disease and for the development of novel diagnostic and therapeutic strategies. | en_GB |
dc.description.sponsorship | Funds have been provided by the Joint Programme—Neurodegenerative Disease Research (JPND) for the EPI-AD consortium focusing on epigenetic dysregulation in the brainstem in Alzheimer’s Disease (http://www.neurodegenerationresearch.eu/wp-content/uploads/2015/10/Factsheet_EPI-AD.pdf). The project is supported through the following funding organizations under the aegis of JPND—http://www.jpnd.eu, The Netherlands, The Netherlands Organisation for Health Research and Development (ZonMw); United Kingdom, Medical Research Council; Germany, German Federal ministry of Education and Research (BMBF); Luxembourg, National Research Fund (FNR). This project has received funding from the European Union’s Horizon 2020 research and innovation programme under Grant Agreement No. 643417. Additional support has been provided by the UK Medical Research Council (MRC) Grant MR/N027973/1 (K.L), Alzheimer’s Association (US) New Investigator Research Grant NIRG-14-320878 (K.L), Alzheimer’s Society (UK) Grant AS-PG-14-038 (K.L), the Internationale Stichting Alzheimer Onderzoek (ISAO) Grants 7551 and 11532 (D.L.A vdH.), the ISAO Grant 12530 (G.K), the ISAO Grant 13515 (B.P.F.R), and the Netherlands Organization for Scientific Research (NWO) Grant 916.11.086 (Veni Award) (B.P.F.R). | en_GB |
dc.identifier.citation | Vol. 74 (3), pp. 509 - 523 | en_GB |
dc.identifier.doi | 10.1007/s00018-016-2361-4 | |
dc.identifier.uri | http://hdl.handle.net/10871/34189 | |
dc.language.iso | en | en_GB |
dc.publisher | Springer Verlag | en_GB |
dc.relation.url | https://www.ncbi.nlm.nih.gov/pubmed/27628303 | en_GB |
dc.rights | © The Author(s) 2016. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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. | en_GB |
dc.subject | Alzheimer’s disease | en_GB |
dc.subject | DNA hydroxymethylation | en_GB |
dc.subject | DNA methylation | en_GB |
dc.subject | Epigenetics | en_GB |
dc.subject | Locus coeruleus | en_GB |
dc.subject | Raphe nuclei | en_GB |
dc.subject | Alzheimer Disease | en_GB |
dc.subject | Animals | en_GB |
dc.subject | Brain Stem | en_GB |
dc.subject | DNA Methylation | en_GB |
dc.subject | Dorsal Raphe Nucleus | en_GB |
dc.subject | Epigenesis, Genetic | en_GB |
dc.subject | Humans | en_GB |
dc.title | Epigenetic dysregulation of brainstem nuclei in the pathogenesis of Alzheimer's disease: looking in the correct place at the right time? | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2018-10-04T10:16:44Z | |
exeter.place-of-publication | Switzerland | en_GB |
dc.description | This is the final version. Available from Springer Verlag via the DOI in this record. | en_GB |
dc.identifier.journal | Cellular and Molecular Life Sciences | en_GB |