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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.

Original publication

DOI

10.1016/j.neurobiolaging.2016.12.029

Type

Journal article

Journal

Neurobiol Aging

Publication Date

05/2017

Volume

53

Pages

36 - 47

Keywords

Alzheimer's disease (AD), Biomarker, Blood, Gene expression, Mild cognitive impairment (MCI), Mitochondria, Oxidative phosphorylation (OXPHOS), Aged, Aged, 80 and over, Alzheimer Disease, Biomarkers, Cognitive Dysfunction, Female, Gene Expression, Genes, Mitochondrial, Humans, Male, Mitochondria, Oxidative Phosphorylation, Reactive Oxygen Species, Transcription, Genetic