Twenty first-order relatives of patients with early-onset Alzheimer’s disease (AD; mean age 43.7 ± 1.3 years), 20 patients with early-onset AD (mean age 65.7 ± 0.9 years) and age-matched normal controls for the relatives and the patients underwent quantitative EEG (qEEG) examinations. In AD patients, delta and theta relative power values were increased and alpha relative power was decreased compared with normal controls. The AD patients’ relatives had normal resting EEG parameters. Under hyperventilation in the AD relatives, synchronous high-voltage delta and theta activity and sharp waves were revealed, theta and delta relative powers were increased and alpha relative power was decreased compared with the resting EEG in the same persons. Moreover, under hyperventilation, the theta and delta relative powers in the EEG of the relatives were higher, and the alpha relative power was lower compared with the EEG of normal controls under the same conditions. It is suggested that the excitotoxic processes and oxidative stress underlie the EEG alterations in the AD patients’ relatives and that these alterations may be related to the further AD development.

Visual-evoked potentials (VEP) to a flash were studied in the first-order relatives of patients with Alzheimer’s disease (AD) (mean age 38.2 ± 2.6 years) in comparison with the patients (mean age 61.9 ± 1.4 years) and age-matched normal controls. It was found that in the relatives of AD patients the latencies of N2, P3, N3 components were delayed compared with the age-matched normal controls. The delay in the latencies of the patients and their relatives concerned the same components but was smaller in the relatives of AD patients. The amplitude of the P2, N2 components was increased in the latter. The neurophysiological alteration in AD patients’ relatives may be considered as signs of a latent neurodegeneration in limbico-reticulo-cortical pathways, which may be connected to the pathological hyperactivity of limbico-reticulo-cortical structures.

Polymorphism in the genomic region harboring the CLU gene (rs11136000) has been associated with the risk for Alzheimer’s disease (AD). CLU C allele is assumed to confer risk for AD and the allele T may have a protective effect. We investigated the influence of the AD-associated CLU genotype on a common neurophysiological trait of brain activity (resting-state alpha-rhythm activity) in non-demented adults and elucidated whether this influence is modified over the course of aging. We examined quantitative EEG (qEEG) in cohort of non-demented individuals (age range 20-80) divided into young (age range 20-50) and old (age range 51-80) cohorts and stratified by CLU polymorphism. To rule out the effect of the ApoE genotype on EEG characteristics, only subjects without the ApoE epsilon4 allele were included in the study. The homozygous presence of the AD risk variant CLU CC in non-demented subjects was associated with an increase of alpha3 absolute power. Moreover, the influence of CLU genotype on alpha3 was found to be higher in the subjects older than 50 years of age. The study also showed age-dependent alterations of alpha topographic distribution that occur independently of the CLU genotype. The increase of upper alpha power has been associated with hippocampal atrophy in patients with mild cognitive impairment (Moretti et al., 2012a). In our study, the CLU CC- dependent increase in upper alpha rhythm, particularly enhanced in elderly non-demented individuals, may imply that the genotype is related to preclinical dysregulation of hippocampal neurophysiology in aging and that this factor may contribute to pathogenesis of AD.

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.