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

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


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).

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / blood*
  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / genetics*
  • Biomarkers / blood
  • Cognitive Dysfunction / blood
  • Cognitive Dysfunction / genetics
  • Female
  • Gene Expression
  • Genes, Mitochondrial / genetics*
  • Humans
  • Male
  • Mitochondria / genetics*
  • Oxidative Phosphorylation
  • Reactive Oxygen Species / metabolism
  • Transcription, Genetic / genetics


  • Biomarkers
  • Reactive Oxygen Species