Genetic association of apolipoprotein E genotype with EEG alpha rhythm slowing and functional brain network alterations during normal aging

Abstract

The ε4 allele of the apolipoprotein E (<i>APOE</i>4+) genotype is a major genetic risk factor for Alzheimer's disease (AD), but the mechanisms underlying its influence remain incompletely understood. The study aimed to investigate the possible effect of the <i>APOE</i> genotype on spontaneous electroencephalogram (EEG) alpha characteristics, resting-state functional MRI (fMRI) connectivity (rsFC) in large brain networks and the interrelation of alpha rhythm and rsFC characteristics in non-demented adults during aging. We examined the EEG alpha subband's relative power, individual alpha peak frequency (IAPF), and fMRI rsFC in non-demented volunteers (age range 26-79 years) stratified by the <i>APOE</i> genotype. The presence of the <i>APOE4+</i> genotype was associated with lower IAPF and lower relative power of the 11-13 Hz alpha subbands. The age related decrease in EEG IAPF was more pronounced in the <i>APOE4+</i> carriers than in the <i>APOE4+</i> non-carriers (<i>APOE4</i>-). The <i>APOE4+</i> carriers had a stronger fMRI positive rsFC of the interhemispheric regions of the frontoparietal, lateral visual and salience networks than the <i>APOE4-</i> individuals. In contrast, the negative rsFC in the network between the left hippocampus and the right posterior parietal cortex was reduced in the <i>APOE4+</i> carriers compared to the non-carriers. Alpha rhythm slowing was associated with the dysfunction of hippocampal networks. Our results show that in adults without dementia <i>APOE4+</i> genotype is associated with alpha rhythm slowing and that this slowing is age-dependent. Our data suggest predominant alterations of inhibitory processes in large-scale brain network of non-demented <i>APOE4+</i> carriers. Moreover, dysfunction of large-scale hippocampal network can influence <i>APOE</i>-related alpha rhythm vulnerability.