AlzBase: an Integrative Database for Gene Dysregulation in Alzheimer's Disease

Abstract

Alzheimer's disease (AD) affects a significant portion of elderly people worldwide. Although the amyloid-β (Aβ) cascade hypothesis has been the prevailing theory for the molecular mechanism of AD in the past few decades, treatment strategies targeting the Aβ cascade have not demonstrated effectiveness as yet. Thus, elucidating the spatial and temporal evolution of the molecular pathways in AD remains to be a daunting task. To facilitate novel discoveries in this filed, here, we have integrated information from multiple sources for the better understanding of gene functions in AD pathogenesis. Several categories of information have been collected, including (1) gene dysregulation in AD and closely related processes/diseases such as aging and neurological disorders, (2) correlation of gene dysregulation with AD severity, (3) a wealth of annotations on the functional and regulatory information, and (4) network connections for gene-gene relationship. In addition, we have also provided a comprehensive summary for the top ranked genes in AlzBase. By evaluating the information curated in AlzBase, researchers can prioritize genes from their own research and generate novel hypothesis regarding the molecular mechanism of AD. To demonstrate the utility of AlzBase, we examined the genes from the genetic studies of AD. It revealed links between the upstream genetic variations and downstream endo-phenotype and suggested several genes with higher priority. This integrative database is freely available on the web at http://alz.big.ac.cn/alzBase .

Keywords: Aging; Brain transcriptome; Genetics; Network; Neurological disorders.