1. Oligomeric amyloid-β peptide affects the expression of genes involved in steroid and lipid metabolism in primary neurons
- Author
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Bilal Malik, Stuart Kellie, C. Hugh Reynolds, Cathy Fernandes, Richard Killick, Ritchie Williamson, Brian H. Anderton, Richard Wroe, and Alessia Usardi
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Genetically modified mouse ,Microarray ,medicine.medical_treatment ,Down-Regulation ,Biology ,Real-Time Polymerase Chain Reaction ,Steroid ,Mice ,Cellular and Molecular Neuroscience ,Biopolymers ,Gene expression ,medicine ,Animals ,Cells, Cultured ,DNA Primers ,Neurons ,Amyloid beta-Peptides ,Base Sequence ,Reverse Transcriptase Polymerase Chain Reaction ,Gene Expression Profiling ,P3 peptide ,Lipid metabolism ,Cell Biology ,Mice, Inbred C57BL ,Gene expression profiling ,Biochemistry ,ABCA1 ,biology.protein - Abstract
Amyloid-β peptide (Aβ) is the principal component of plaques in the brains of patients with Alzheimer's disease (AD), and the most toxic form of Aβ may be as soluble oligomers. We report here the results of a microarray study of gene expression profiles in primary mouse cortical neurons in response to oligomeric Aβ(1-42). A major and unexpected finding was the down-regulation of genes involved in the biosynthesis of cholesterol and other steroids and lipids (such as Fdft1, Fdps, Idi1, Ldr, Mvd, Mvk, Nsdhl, Sc4mol), the expression of which was verified by quantitative real-time RT-PCR (qPCR). The ATP-binding cassette gene Abca1, which has a major role in cholesterol transport in brain and other tissues and has been genetically linked to AD, was notably up-regulated. The possible involvement of cholesterol and other lipids in Aβ synthesis and action in Alzheimer's disease has been studied and debated extensively but remains unresolved. These new data suggest that Aβ may influence steroid and lipid metabolism in neurons via multiple gene-expression changes.
- Published
- 2012
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