Modeling the interactions of Alzheimer-related genes from the whole brain microarray data and diffusion tensor images of human brain

BACKGROUND: In recent years the genome-wide microarray-based gene expression profiles and diffusion tensor images (DTI) in human brain have been made available with accompanying anatomic and histology data. The challenge is to integrate various types of data to investigate the interactions of genes that are associated with specific neurological disorder. RESULTS: In this study, we analyzed the whole brain microarray data and the physical connectivity of the hippocampus with other brain regions to identify the genes related to Alzheimer's disease and their interactions with proteins. We generated a physical connectivity map of the left and right hippocampuses with 12 other brain regions and identified 33 Alzheimer-related genes that interact with many proteins. These genes are highly linked to the development of Alzheimer's disease. CONCLUSIONS: In Alzheimer's brain both brain regions and inter-regional communications through the white matter are often hampered. So far the connectivity of regions in Alzheimer's brain has been studied mostly at the functional level using functional MRI (fMRI). Analyzing the inter-regional fiber connectivity without tracking crossing-fiber regions often provides coarse and inaccurate results. A few deep brain fibers were analyzed but the inter-regional fiber connectivity was not analyzed in their studies. The inter-regional fiber connectivity analysis can provide comprehensive and measurable degradation of fiber tracts in AD patients' brains, but is not easy to perform. We tracked crossing-fiber regions and identified genes with high expression levels in the fiber pathways of the hippocampus. The interactions of the genes with other proteins can provide comprehensive and measurable degradation of fiber tracts in Alzheimer brains. To the best of our knowledge, this is the first attempt to integrate the whole brain microarray data with DTI data to identify specific genes and their interactions.