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

The ε4 allele of the apolipoprotein E (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 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 genotype. The presence of the 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 carriers than in the non-carriers (-). The carriers had a stronger fMRI positive rsFC of the interhemispheric regions of the frontoparietal, lateral visual and salience networks than the individuals. In contrast, the negative rsFC in the network between the left hippocampus and the right posterior parietal cortex was reduced in the 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 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 carriers. Moreover, dysfunction of large-scale hippocampal network can influence -related alpha rhythm vulnerability.