Mitochondrial genes are altered in blood early in Alzheimer's disease.
Τίτλος | Mitochondrial genes are altered in blood early in Alzheimer's disease. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Lunnon, K., Keohane A., Pidsley R., Newhouse S., Riddoch-Contreras J., Thubron E. B., Devall M., Soininen H., Kłoszewska I., Mecocci P., Tsolaki M., Vellas B., Schalkwyk L., Dobson R., Malik A. N., Powell J., Lovestone S., & Hodges A. |
Corporate Authors | AddNeuroMed Consortium |
Journal | Neurobiol Aging |
Volume | 53 |
Pagination | 36-47 |
Date Published | 2017 05 |
ISSN | 1558-1497 |
Λέξεις κλειδιά | 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 |
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. |
DOI | 10.1016/j.neurobiolaging.2016.12.029 |
Alternate Journal | Neurobiol. Aging |
PubMed ID | 28208064 |
Grant List | / / British Heart Foundation / United Kingdom / / Medical Research Council / United Kingdom / / Cancer Research UK / United Kingdom G0801464 / / Medical Research Council / United Kingdom MR/K006584/1 / / Wellcome Trust / United Kingdom / / Arthritis Research UK / United Kingdom / / Chief Scientist Office / United Kingdom |