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

Lunnon, K and Keohane, A and Pidsley, R and Newhouse, S and Riddoch-Contreras, J and Thubron, EB and Devall, M and Soininen, H and Kłoszewska, I and Mecocci, P and Tsolaki, M and Vellas, B and Schalkwyk, L and Dobson, R and Malik, AN and Powell, J and Lovestone, S and Hodges, A (2017) 'Mitochondrial genes are altered in blood early in Alzheimer's disease.' Neurobiology of Aging, 53. 36 - 47. ISSN 0197-4580

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© 2017 The Author(s) 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
Subjects: Q Science > QH Natural history > QH426 Genetics
Divisions: Faculty of Science and Health > Biological Sciences, School of
Depositing User: Leonard Schalkwyk
Date Deposited: 19 Jan 2017 15:19
Last Modified: 31 Oct 2017 11:15

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