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Oligomeric amyloid β preferentially targets neuronal and not glial mitochondrial‐encoded mRNAs
Author(s) -
Mastroeni Diego,
Nolz Jennifer,
Khdour Omar M.,
Sekar Shobana,
Delvaux Elaine,
Cuyugan Lori,
Liang Winnie S.,
Hecht Sidney M.,
Coleman Paul D.
Publication year - 2018
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2017.12.005
Subject(s) - laser capture microdissection , microglia , mitochondrion , transcriptome , amyloid beta , alzheimer's disease , hippocampal formation , microbiology and biotechnology , biology , reactive oxygen species , chemistry , neuroscience , biochemistry , gene expression , pathology , medicine , disease , gene , inflammation , immunology , peptide
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.