Nuclear but not mitochondrial-encoded oxidative phosphorylation genes are altered in aging, mild cognitive impairment, and Alzheimer's disease

We have comprehensively described the expression profiles of mitochondrial DNA and nuclear DNA genes that encode subunits of the respiratory oxidative phosphorylation (OXPHOS) complexes (I–V) in the hippocampus from young controls, age matched, mild cognitively impaired (MCI), and Alzheimer's d...

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Published inAlzheimer's & dementia Vol. 13; no. 5; pp. 510 - 519
Main Authors Mastroeni, Diego, Khdour, Omar M., Delvaux, Elaine, Nolz, Jennifer, Olsen, Gary, Berchtold, Nicole, Cotman, Carl, Hecht, Sidney M., Coleman, Paul D.
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 01.05.2017
Subjects
Adult
Aged, 80 and over
Aging
Aging - genetics
Alzheimer Disease - genetics
Alzheimer's disease
Autopsy
Cognition Disorders - genetics
Female
Hippocampus
Humans
Male
Microarray
Mild cognitively impaired (MCI)
Mitochondria
Mitochondria - genetics
Oligonucleotide Array Sequence Analysis
Oxidative Phosphorylation
Oxidative phosphorylation-related genes expression
Postmortem brains
Mitochondria
Oxidative phosphorylation-related genes expression
Aging
Postmortem brains
Microarray
Alzheimer's disease
Mild cognitively impaired (MCI)
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Summary:We have comprehensively described the expression profiles of mitochondrial DNA and nuclear DNA genes that encode subunits of the respiratory oxidative phosphorylation (OXPHOS) complexes (I–V) in the hippocampus from young controls, age matched, mild cognitively impaired (MCI), and Alzheimer's disease (AD) subjects. Hippocampal tissues from 44 non-AD controls (NC), 10 amnestic MCI, and 18 AD cases were analyzed on Affymetrix Hg-U133 plus 2.0 arrays. The microarray data revealed significant down regulation in OXPHOS genes in AD, particularly those encoded in the nucleus. In contrast, there was up regulation of the same gene(s) in MCI subjects compared to AD and ND cases. No significant differences were observed in mtDNA genes identified in the array between AD, ND, and MCI subjects except one mt-ND6. Our findings suggest that restoration of the expression of nuclear-encoded OXPHOS genes in aging could be a viable strategy for blunting AD progression.
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ISSN:1552-5260
1552-5279
DOI:10.1016/j.jalz.2016.09.003