Effect of MAPT gene variations on the brain electrical activity: A multiplex network study

The aim of this study is to examine how variations in the microtubule-associated protein tau ( MAPT ) gene affect the brain functional network. For this purpose, resting-state electroencephalogram (EEG) data from 155 participants were acquired. This database included healthy controls and Alzheimer’s disease patients carrying seven MAPT alleles associated with risk or protective effects against neuropathologies or abnormal tau levels. To assess the impact of each genotype on brain function, a multiplex network analysis quantified the connectivity contribution of each brain region across multiple EEG frequency bands: (delta, theta, alpha, and beta). To this end, brain functional connectivity was first calculated for each brain region and frequency band using the phase lag index (PLI) parameter. The PLI adjacency matrices in each frequency band corresponded to the layers conforming the multiplex network. Subsequently, the participation coefficient ( P ) was computed in each brain region to reflect node degree diversification among frequency bands. Carriers of risk and protective alleles exhibited distinct values of P , especially in the left default mode network in healthy controls. In addition, carriers of the risk alleles generally presented higher network disruptions. Finally, significant differences in node degree values were observed across SNPs in the theta and beta frequency bands. These results suggest that different MAPT variants may lead to diverse tau species that influence brain function, particularly in brain regions involved in information flow management in preclinical states. These insights may help understanding network disturbances caused by molecular factors. • MAPT variations are associated with alterations in brain connectivity patterns. • The left default mode network is particularly sensitive to MAPT genotypes. • Differences in tau expression may be the cause of brain activity disruptions.