Dysregulation of inter-tissue gene co-expression networks in Alzheimer’s Disease

This study aims to understand the inter-tissue network of gene-gene interactions at the transcriptional level, we developed a framework to statistically infer the underlying correlation (co-expression) network structure among genes in different brain tissues and the rewiring of this gene co-expression network between healthy vs. diseased groups of individuals. We applied this framework to infer inter-tissue interactions in Alzheimer’s Disease (AD) across four different brain regions - Frontal pole, Superior temporal gyrus, Para-hippocampal gyrus, and Inferior frontal gyrus - by utilizing gene expression data available on these brains tissues/regions collected post-mortem from about 225 AD individuals with varying disease severity and 100 healthy controls. The resulting genes and inter-tissue gene pairs dysregulated in AD are compared against known AD-related genes and protein biomarkers to assess their biological relevance, and known cell type-specific marker genes to estimate the frequency of different brain cell types in each individual and thereby assess the effect of cellular composition on the identified inter-tissue gene networks.