Oligomeric amyloid β preferentially targets neuronal and not glial mitochondrial-encoded mRNAs

Diego Mastroeni, Jennifer Nolz, Omar Khdour, Shobana Sekar, Elaine Delvaux, Lori Cuyugan, Winnie S. Liang, Sidney Hecht, Paul Coleman

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Introduction: Our laboratories have demonstrated that accumulation of oligomeric amyloid β (OAβ) in neurons is an essential step leading to OAβ-mediated mitochondrial dysfunction. Methods: Alzheimer's disease (AD) and matching control hippocampal neurons, astrocytes, and microglia were isolated by laser-captured microdissection from the same subjects, followed by whole-transcriptome sequencing. Complementary in vitro work was performed in OAβ-treated differentiated SH-SY5Y, followed by the use of a novel CoQ10 analogue for protection. This compound is believed to be effective both in suppressing reactive oxygen species and also functioning in mitochondrial electron transport. Results: We report decreases in the same mitochondrial-encoded mRNAs in Alzheimer's disease laser-captured CA1 neurons and in OAβ-treated SH-SY5Y cells, but not in laser-captured microglia and astrocytes. Pretreatment with a novel CoQ10 analogue, protects neuronal mitochondria from OAβ-induced mitochondrial changes. Discussion: Similarity of expression changes in neurons from Alzheimer's disease brain and neuronal cells treated with OAβ, and the effect of a CoQ10 analogue on the latter, suggests a pretreatment option to prevent OAβ toxicity, long before the damage is apparent.

Original languageEnglish (US)
JournalAlzheimer's and Dementia
DOIs
StateAccepted/In press - Jan 1 2018

Keywords

  • Alzheimer's disease
  • Laser capture microdissection
  • Mitochondria
  • Multifunctional radical quencher
  • Oligomeric amyloid β

ASJC Scopus subject areas

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

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