Spectral graph theory and graph energy metrics show evidence for the alzheimer´s disease disconnection syndrome in APOE-4 risk gene carriers

Our understanding of network breakdown in Alzheimer´s disease (AD) is likely to be enhanced through advanced mathematical descriptors. Here, we applied spectral graph theory to provide novel metrics of structural connectivity based on 3-Tesla diffusion weighted images in 42 AD patients and 50 healthy controls. We reconstructed connectivity networks using whole-brain tractography and examined, for the first time here, cortical disconnection based on the graph energy and spectrum. We further assessed supporting metrics - link density and nodal strength - to better interpret our results. Metrics were analyzed in relation to the well-known APOE-4 genetic risk factor for late-onset AD. The number of disconnected cortical regions increased with the number of copies of the APOE-4 risk gene in people with AD. Each additional copy of the APOE-4 risk gene may lead to more dysfunctional networks with weakened or abnormal connections, providing evidence for the previously hypothesized “disconnection syndrome”.