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 CoQ 10 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 CoQ 10 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 CoQ 10 analogue on the latter, suggests a pretreatment option to prevent OAβ toxicity, long before the damage is apparent.
Original language | English (US) |
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Pages (from-to) | 775-786 |
Number of pages | 12 |
Journal | Alzheimer's and Dementia |
Volume | 14 |
Issue number | 6 |
DOIs | |
State | Published - Jun 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
- Psychiatry and Mental health
- Cellular and Molecular Neuroscience