Lunnon, K;
Keohane, A;
Pidsley, R;
Newhouse, S;
Riddoch-Contreras, J;
Thubron, EB;
Devall, M;
... Hodges, A; + view all
(2017)
Mitochondrial genes are altered in blood early in Alzheimer's disease.
Neurobiology of Aging
, 53
pp. 36-47.
10.1016/j.neurobiolaging.2016.12.029.
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Abstract
Although mitochondrial dysfunction is a consistent feature of Alzheimer's disease 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 Alzheimer's disease and mild cognitive impairment. 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 that 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.
| Type: | Article |
|---|---|
| Title: | Mitochondrial genes are altered in blood early in Alzheimer's disease |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.neurobiolaging.2016.12.029 |
| Publisher version: | https://doi.org/10.1016/j.neurobiolaging.2016.12.0... |
| Language: | English |
| Additional information: | © 2017 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Geriatrics & Gerontology, Neurosciences, Neurosciences & Neurology, Mitochondria, Alzheimer's Disease (AD), Gene Expression, Blood, Biomarker, Mild Cognitive Impairment (MCI), Oxidative Phosphorylation (Oxphos), Mild Cognitive Impairment, Cytochrome-C-Oxidase, Oxidative Damage, Brain, Lymphocytes, Expression, DNA, Dysfunction, Platelets, Neurodegeneration |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics > Clinical Epidemiology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1552420 |
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