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Neurobiol Aging. 2017 May;53:36-47. doi: 10.1016/j.neurobiolaging.2016.12.029. Epub 2017 Jan 7.

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

Author information

1
Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; University of Exeter Medical School, University of Exeter, Devon, UK.
2
Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
3
Diabetes Research Group, Faculty of Life Sciences and Medicine, King's College London, London, UK.
4
University of Exeter Medical School, University of Exeter, Devon, UK.
5
Department of Neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
6
Medical University of Lodz, Lodz, Poland.
7
Institute of Gerontology and Geriatrics, University of Perugia, Perugia, Italy.
8
3rd Department of Neurology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
9
INSERM U 558, University of Toulouse, Toulouse, France.
10
Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. Electronic address: angela.k.hodges@kcl.ac.uk.

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.

KEYWORDS:

Alzheimer's disease (AD); Biomarker; Blood; Gene expression; Mild cognitive impairment (MCI); Mitochondria; Oxidative phosphorylation (OXPHOS)

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