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

Lunnon, Katie and Keohane, Aoife and Pidsley, Ruth and Newhouse, Stephen and Riddoch-Contreras, Joanna and Thubron, Elisabeth B and Devall, Matthew and Soininen, Hikka and Kłoszewska, Iwona and Mecocci, Patrizia and Tsolaki, Magda and Vellas, Bruno and Schalkwyk, Leonard and Dobson, Richard and Malik, Afshan N and Powell, John and Lovestone, Simon and Hodges, Angela (2017) 'Mitochondrial genes are altered in blood early in Alzheimer's disease.' Neurobiology of Aging, 53. pp. 36-47. ISSN 0197-4580

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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.

Item Type: Article
Uncontrolled Keywords: Mitochondria; Alzheimer's disease (AD); Gene expression; Blood; Biomarker; Mild cognitive impairment (MCI); Oxidative phosphorylation (OXPHOS)
Subjects: Q Science > QH Natural history > QH426 Genetics
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 19 Jan 2017 15:19
Last Modified: 18 Aug 2022 11:39
URI: http://repository.essex.ac.uk/id/eprint/18785

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