title: Oligomeric amyloid-β peptide affects the expression of genes involved in steroid and lipid metabolism in primary neurons.
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.
authors.affiliation: KHP Centre for Neurodegeneration Research, King's College London, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF, UK. b.malik@ucl.ac.uk
authors.forename: Bilal
authors.initials: B
authors.lastname: Malik
authors.forename: Cathy
authors.initials: C
authors.lastname: Fernandes
authors.forename: Richard
authors.initials: R
authors.lastname: Killick
authors.forename: Richard
authors.initials: R
authors.lastname: Wroe
authors.forename: Alessia
authors.initials: A
authors.lastname: Usardi
authors.forename: Ritchie
authors.initials: R
authors.lastname: Williamson
authors.forename: Stuart
authors.initials: S
authors.lastname: Kellie
authors.forename: Brian H
authors.initials: BH
authors.lastname: Anderton
authors.forename: C Hugh
authors.initials: CH
authors.lastname: Reynolds
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D001483:Base Sequence; D001704:Biopolymers; D002478:Cells, Cultured; D017931:DNA Primers; D015536:Down-Regulation; D020869:Gene Expression Profiling; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016229:Amyloid beta-Peptides; D001704:Biopolymers; D017931:DNA Primers