Brain topology alteration in Alzheimer’s disease brain networks: A multi-center study

Alterations in brain network centrality are key features of Alzheimer's disease (AD) and may offer insights into the disruption of network organization underlying cognitive decline. We introduce a novel centrality metric, DomiRank, to characterize dominance-driven connectivity patterns in the human brain network, using a multi-center MRI dataset comprising 809 participants. Compared with conventional metrics, DomiRank centrality showed greater sensitivity in detecting AD-related network disruptions, particularly within the cingulate gyrus, precuneus, and subcortical hubs such as the basal ganglia-regions critical for cognition. Regional DomiRank alterations were significantly correlated with clinical cognitive scores, indicating their potential relevance to disease severity. Gene enrichment analysis revealed that areas with reduced DomiRank centrality were enriched for genes involved in synaptic signaling and neuronal communication, suggesting molecular mechanisms underlying network vulnerability. These findings highlight DomiRank centrality as a promising biomarker for characterizing network disorganization in AD, linking changes in brain connectivity with underlying molecular processes.