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 (APOE4+) 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 APOE 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 APOE genotype. The presence of the APOE4+ 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 APOE4+ carriers than in the APOE4+ non-carriers (APOE4-). The APOE4+ carriers had a stronger fMRI positive rsFC of the interhemispheric regions of the frontoparietal, lateral visual and salience networks than the APOE4– individuals. In contrast, the negative rsFC in the network between the left hippocampus and the right posterior parietal cortex was reduced in the APOE4+ 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 APOE4+ 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 APOE4+ carriers. Moreover, dysfunction of large-scale hippocampal network can influence APOE-related alpha rhythm vulnerability.

Abnormal Temporal Slowing on EEG Findings in Preclinical Alzheimer’s Disease Patients With the ApoE4 Allele: A Pilot Study

“…Although our study focused on temporal slowing, it is crucial to consider other EEG features when evaluating individuals at risk for AD. For instance, one study reported a relationship between the presence of ApoE4 and increased alpha rhythm slowing [22]. Considering the multitude of EEG factors, further research is needed to comprehensively assess the utility of EEG in preclinical AD patients.…”

Cross-Subject Classification of Effectiveness in Performing Cognitive Tasks Using Resting-State EEG

“…The spectral power of resting-state EEG frequency bands demonstrated a higher heritability in a large cohort in twin studies [15,16]. Moreover, some frequency patterns of spontaneous brain oscillations correlated with specific genotypes in healthy aging [17]. In parallel, fMRI studies showed that individual spontaneous neural activity at rest is correlated with functionally active networks and cognitive performance suggesting that patterns of resting-state activity could be explored as endophenotypes of cognitive abilities [18,19].…”

Neuronal Hyperactivation in EEG Data during Cognitive Tasks Is Related to the Apolipoprotein J/Clusterin Genotype in Nondemented Adults

“…Research has demonstrated an association between QEEG parameters and AD risk variants in the APOE , CLU , PICALM , IL1RAP , UNC5C , and NAV2 genes in AD [ 38 , 39 , 40 , 41 , 42 ] and MCI patients [ 43 , 44 , 45 ] as well as in healthy adults [ 46 , 47 , 48 , 49 , 50 ]. Moreover, the association of neurophysiological parameters with AD-related genetic factors was shown to be age dependent.…”