Gene expression profile and functional analysis of Alzheimer's disease.

Abstract

Alzheimer's disease (AD) is a complex neurodegenerative disorder with largely unknown genetic mechanisms. Identifying altered neuronal gene expression in brain regions differentially affected by AD may provide the diagnostic or therapeutic targets of AD. The gene expression profile of AD was analyzed with bioinformatics. Function analysis was performed with Database for Annotation, Visualization and Integrated Discovery (DAVID), and TransFind was used to predict the possible transcriptional regulators in AD. Finally, connectivity map (cMap) database was used to explore small molecules targeted for AD. The AD gene signatures associated with 6 different brain regions were identified. Functional analysis revealed that biological processes involved with metabolism, protein ubiquitination, and vasculature development were found dysregulated, and synaptic signaling pathways were found perturbated in AD. The WT1 was identified as an important transcriptional regulator in AD, and cMap database predicted that small molecules, such as histone deacetylase (HDAC) inhibitor, may be candidate drugs in the treatment of AD. According to our in silico analysis, Wilms' tumor suppressor may play regulatory roles in AD development and progress. The HDAC inhibitor could possibly be used to treat AD.