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

BackgroundA typical pathological feature of Alzheimer's disease (AD) is the appearance in the brain of senile plaques made up of β-amyloid (Aβ) 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 Aβ aggregation and neurotoxicity. MethodologyIn this study, employing a microarray analysis of 35,129 genes, we investigated the effects induced by the exposure to the Aβ1–42-Al (Aβ-Al) complex on the gene expression profile of the neuronal-like cell line, SH-SY5Y. Principal FindingsThe microarray assay indicated that, compared to Aβ or Al alone, exposure to Aβ-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 SignificanceAβ-Al appears to be largely involved in the molecular machinery that regulates neuronal as well as synaptic dysfunction and loss. Aβ-Al seems critical in modulating key AD-related pathways such as glutamatergic transmission, Ca2+ homeostasis, oxidative stress, inflammation, and neuronal apoptosis.