Oligomeric amyloid-β peptide affects the expression of genes involved in steroid and lipid metabolism in primary neurons

• Published in: Neurochemistry international 2012-08, Vol.61 (3), p.321-333
• Main Authors: Malik, Bilal, Fernandes, Cathy, Killick, Richard, Wroe, Richard, Usardi, Alessia, Williamson, Ritchie, Kellie, Stuart, Anderton, Brian H., Reynolds, C. Hugh
• Format: Article
• Language: English
• Subjects: ADDLs; Amyloid beta-Peptides - metabolism; Amyloid beta-Peptides - physiology; Amyloid β oligomers; Animals; Base Sequence; Biological and medical sciences; Biopolymers; Cells, Cultured; Cholesterol; DNA Primers; Down-Regulation; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Profiling; Mice; Mice, Inbred C57BL; Microarray; Neurons - metabolism; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Steroid metabolism; Vertebrates: nervous system and sense organs
• ISSN: 0197-0186; 1872-9754
• DOI: 10.1016/j.neuint.2012.05.006

► Microarray study of primary mouse cortical neurons treated with oligomeric Aβ1–42 (ADDLs). ► Down-regulation of genes involved in the biosynthesis of cholesterol and other steroids/lipids. ► Abca1, involved in cholesterol transport and linked to Alzheimer’s, up-regulated. ► Interactions between Aβ and cholesterol potentially important in Alzheimer’s pathology. 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 Aβ1–42. 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.