Microarray Analysis on Human Neuroblastoma Cells Exposed to Aluminum, β1-42-Amyloid or the β1-42-Amyloid Aluminum Complex

Background: A typical pathological feature of Alzheimer's disease (AD) is the appearance in the brain of senile plaques made up of beta-amyloid (A beta) and neurofibrillary tangles. AD is also associated with an abnormal accumulation of some metal ions, and we have recently shown that one of these, aluminum (Al), plays a relevant role in affecting A beta aggregation and neurotoxicity. Methodology: In this study, employing a microarray analysis of 35,129 genes, we investigated the effects induced by the exposure to the A beta(1-42)-Al (A beta-Al) complex on the gene expression profile of the neuronal-like cell line, SH-SY5Y. Principal Findings: The microarray assay indicated that, compared to A beta or Al alone, exposure to A beta-Al complex produced selective changes in gene expression. Some of the genes selectively over or underexpressed are directly related to AD. A further evaluation performed with Ingenuity Pathway analysis revealed that these genes are nodes of networks and pathways that are involved in the modulation of Ca2+ homeostasis as well as in the regulation of glutamatergic transmission and synaptic plasticity. Conclusions and Significance: A beta-Al appears to be largely involved in the molecular machinery that regulates neuronal as well as synaptic dysfunction and loss. A beta-Al seems critical in modulating key AD-related pathways such as glutamatergic transmission, Ca2+ homeostasis, oxidative stress, inflammation, and neuronal apoptosis.