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

Research output: Contribution to journalArticle

Katie Lunnon, Aoife Keohane, Ruth Pidsley, Stephen Newhouse, Joanna Riddoch-Contreras, Elisabeth B. Thubron, Matthew Devall, Hikka Soininen, Iwona Kłoszewska, Patrizia Mecocci, Magda Tsolaki, Bruno Vellas, Leonard Schalkwyk, Richard Dobson, Afshan N. Malik, John Powell, Simon Lovestone, Angela Hodges

Original languageEnglish
Pages (from-to)36-47
Number of pages12
JournalNeurobiology of Aging
Volume53
Early online date7 Jan 2017
DOIs
StatePublished - 1 May 2017

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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.

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