Genetic association of apolipoprotein E genotype with EEG alpha rhythm and resting‐state functional MRI connectivity in non‐demented adults during aging

Abstract

AbstractBackgroundThe ε4 allele of the apolipoprotein E (APOE) genotype is a major genetic risk factor for Alzheimer’s disease (AD), but the mechanisms underlying its influence are not completely understood. The study was aimed at determining the possible effect of APOE genotype on spontaneous EEG alpha rhythm characteristics and on the resting‐state functional MRI (fMRI) connectivity (rsFC) in large brain networks in non‐demented adults during aging.MethodWe examined individual alpha peak frequency (IAPF), the EEG alpha sub‐bands power and the fMRI rsFC in 137 non‐demented volunteers, age range 26‐79 years, stratified by APOE genotype. APOE ε3/ε3 subgroup (APOE4‐) included 91 subjects, APOE ε4/ε3+ (APOE4+) subgroup – 46 subjects. The individuals underwent resting‐state fMRI of the brain, the CONN Matlab/SPM‐based toolbox was used to study connectivity in brain networks (Whitfield‐Gabrieli and Nieto‐Castanon, 2012). Informed written consent was obtained from all participants. All subjects underwent a neurological examination and cognitive screening.ResultThe presence of the APOE4+ genotype was associated with lower IAPF and lower relative power of the 11‐13Hz alpha sub‐bands. The age‐related alpha rhythm slowing was more pronounced in the APOE4+ than in the APOE4+ non‐carriers. The negative rsFC between the left hippocampus and the right posterior parietal cortex was reduced for the APOE4+ carriers compared to the APOE4‐ carriers. EEG IAFT showed a significant inverse correlation between rsFC of the left hippocampus and the right posterior parietal cortex.ConclusionAPOE4+ genotype is associated with marked age‐related alpha rhythm slowing and the dysfunction of the inhibitory large‐scale hippocampal networks. Inhibitory deficit of these networks function, interconnected with alpha rhythm slowing, may be related to learning and memory impairments and contribute to the subsequent AD development.This study was supported by Russian Science Foundation (Project No. 19‐75‐30039, genotyping)