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

Amyloid-beta peptide (A beta) is the principal component of plaques in the brains of patients with Alzheimer's disease (AD), and the most toxic form of A beta 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 A beta(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 A beta synthesis and action in Alzheimer's disease has been studied and debated extensively but remains unresolved. These new data suggest that A beta may influence steroid and lipid metabolism in neurons via multiple gene-expression changes. (c) 2012 Elsevier Ltd. All rights reserved.