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Reference: Lunnon, K, Keohan, A, Pidsley, R et al., (2017). Mitochondrial genes are altered in blood early in Alzheimer's disease. Neurobiology of Aging, 53, 36–47.Citable link to this page:

 

Mitochondrial genes are altered in blood early in Alzheimer's disease

Abstract: Although mitochondrial dysfunction is a consistent feature of Alzheimer's disease (AD) in the brain and blood, the molecular mechanisms behind these phenomena are unknown. Here we have replicated our previous findings demonstrating reduced expression of nuclear-encoded oxidative phosphorylation (OXPHOS) subunits and subunits required for the translation of mitochondrial-encoded OXPHOS genes in blood from people with AD and mild cognitive impairment (MCI). Interestingly this was accompanied by increased expression of some mitochondrial-encoded OXPHOS genes, namely those residing closest to the transcription start site of the polycistronic heavy chain mitochondrial transcript (MT-ND1, MT-ND2, MT-ATP6, MT-CO1, MT-CO2, MT-C03) and MT-ND6 transcribed from the light chain. Further we show that mitochondrial DNA copy number was unchanged suggesting no change in steady-state numbers of mitochondria. We suggest an imbalance in nuclear and mitochondrial genome-encoded OXPHOS transcripts may drive a negative feedback loop reducing mitochondrial translation and compromising OXPHOS efficiency, which is likely to generate damaging reactive oxygen species (ROS).

Publication status:PublishedPeer Review status:Peer reviewedVersion:Publisher's versionDate of acceptance:08 January 2017 Funder: European Commission   Funder: Alzheimer’s Research UK   Funder: John and Lucille van Geest Foundation   Funder: Rosetrees Trust   Funder: National Institute for Health Research   Notes:Copyright © 2017 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-NDlicense (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Bibliographic Details

Publisher: Elsevier

Publisher Website: http://www.elsevier.com/

Journal: Neurobiology of Agingsee more from them

Publication Website: https://www.journals.elsevier.com/neurobiology-of-aging

Volume: 53

Extent: 36–47

Issue Date: 2017

pages:36–47Identifiers

Doi: https://doi.org/10.1016/j.neurobiolaging.2016.12.029

Uuid: uuid:a01bd869-f336-4935-a08a-a91f64ac2492

Urn: uri:a01bd869-f336-4935-a08a-a91f64ac2492

Pubs-id: pubs:668949

Issn: 0197-4580

Eissn: 1558-1497 Item Description

Type: journal-article;

Version: Publisher's versionKeywords: mitochondria Alzheimer's disease AD gene expression blood biomarker mild cognitive impairment MCI oxidative phosphorylation OXPHOS

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Autor: Lunnon, K - - - Keohan, A - - - Pidsley, R - - - Newhouse, S - - - Riddoch-Contreras, J - - - Thubron, EB - - - Devall, M - - - S

Fuente: https://ora.ox.ac.uk/objects/uuid:a01bd869-f336-4935-a08a-a91f64ac2492



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