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

Diego Mastroeni, Omar Khdour, Elaine Delvaux, Jennifer Nolz, Gary Olsen, Nicole Berchtold, Carl Cotman, Sidney Hecht, Paul Coleman

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Introduction: 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. Methods: 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. Results: 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. Discussion: Our findings suggest that restoration of the expression of nuclear-encoded OXPHOS genes in aging could be a viable strategy for blunting AD progression.

Original languageEnglish (US)
JournalAlzheimer's and Dementia
DOIs
StateAccepted/In press - 2016

Fingerprint

Oxidative Phosphorylation
Alzheimer Disease
Genes
Mitochondrial DNA
Disease Progression
Cognitive Dysfunction
Hippocampus
Up-Regulation
Down-Regulation
DNA

Keywords

  • Aging
  • Alzheimer's disease
  • Microarray
  • Mild cognitively impaired (MCI)
  • Mitochondria
  • Oxidative phosphorylation-related genes expression
  • Postmortem brains

ASJC Scopus subject areas

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Geriatrics and Gerontology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health

Cite this

Nuclear but not mitochondrial-encoded OXPHOS genes are altered in aging, mild cognitive impairment, and Alzheimer's disease. / Mastroeni, Diego; Khdour, Omar; Delvaux, Elaine; Nolz, Jennifer; Olsen, Gary; Berchtold, Nicole; Cotman, Carl; Hecht, Sidney; Coleman, Paul.

In: Alzheimer's and Dementia, 2016.

Research output: Contribution to journalArticle

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AU - Mastroeni, Diego

AU - Khdour, Omar

AU - Delvaux, Elaine

AU - Nolz, Jennifer

AU - Olsen, Gary

AU - Berchtold, Nicole

AU - Cotman, Carl

AU - Hecht, Sidney

AU - Coleman, Paul

PY - 2016

Y1 - 2016

N2 - Introduction: 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. Methods: 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. Results: 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. Discussion: Our findings suggest that restoration of the expression of nuclear-encoded OXPHOS genes in aging could be a viable strategy for blunting AD progression.

AB - Introduction: 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. Methods: 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. Results: 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. Discussion: 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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KW - Alzheimer's disease

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KW - Postmortem brains

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