title: Mitochondrial genes are altered in blood early in Alzheimer's disease.
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.
authors.affiliation: Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; University of Exeter Medical School, University of Exeter, Devon, UK.
authors.forename: Katie
authors.initials: K
authors.lastname: Lunnon
authors.affiliation: Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: Aoife
authors.initials: A
authors.lastname: Keohane
authors.affiliation: Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: Ruth
authors.initials: R
authors.lastname: Pidsley
authors.affiliation: Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Newhouse
authors.affiliation: Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: Joanna
authors.initials: J
authors.lastname: Riddoch-Contreras
authors.affiliation: Diabetes Research Group, Faculty of Life Sciences and Medicine, King's College London, London, UK.
authors.forename: Elisabeth B
authors.initials: EB
authors.lastname: Thubron
authors.affiliation: University of Exeter Medical School, University of Exeter, Devon, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Devall
authors.affiliation: Department of Neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
authors.forename: Hikka
authors.initials: H
authors.lastname: Soininen
authors.affiliation: Medical University of Lodz, Lodz, Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Kłoszewska
authors.affiliation: Institute of Gerontology and Geriatrics, University of Perugia, Perugia, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Mecocci
authors.affiliation: 3rd Department of Neurology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Magda
authors.initials: M
authors.lastname: Tsolaki
authors.affiliation: INSERM U 558, University of Toulouse, Toulouse, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Vellas
authors.affiliation: Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: Leonard
authors.initials: L
authors.lastname: Schalkwyk
authors.affiliation: Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Dobson
authors.affiliation: Diabetes Research Group, Faculty of Life Sciences and Medicine, King's College London, London, UK.
authors.forename: Afshan N
authors.initials: AN
authors.lastname: Malik
authors.affiliation: Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: John
authors.initials: J
authors.lastname: Powell
authors.affiliation: Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Lovestone
authors.affiliation: Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. Electronic address: angela.k.hodges@kcl.ac.uk.
authors.forename: Angela
authors.initials: A
authors.lastname: Hodges
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000175:diagnosis / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D060825:Cognitive Dysfunction / Q000097:blood / Q000235:genetics; D005260:Female; D015870:Gene Expression; D050259:Genes, Mitochondrial / Q000235:genetics*; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000235:genetics*; D010085:Oxidative Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D015415:Biomarkers; D017382:Reactive Oxygen Species
keywords: Alzheimer's disease (AD); Biomarker; Blood; Gene expression; Mild cognitive impairment (MCI); Mitochondria; Oxidative phosphorylation (OXPHOS)