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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.

More than 100 point mutations spanning the 153 amino acid SOD1 sequence have been identified in individuals with ALS. In 1999 the Amyotrophic Lateral Sclerosis Database (ALSOD) was generated to store these mutations along with ALS patient information to facilitate the identification of a correlation between the SOD1 genotype with the ALS phenotype. Here we report our ongoing development and redesign of the ALSOD database and its automated procedures. The significant new features have improved ALSOD, helping link the mutations of the SOD1 gene to the hypothetical three-dimensional protein structural rearrangement, and the resulting ALS phenotype. Additionally, ALSOD now provides a more comprehensive knowledge base for ALS, detailing genetic, proteomic, and bioinformatics information associated with the disease. ALSOD can be accessed at http://alsod.iop.kcl.ac.uk/als/.