Association of GAB2 genotype with EEG characteristics and vascular reactivity to hyperventilation in nondemented adults during aging

Abstract

AbstractBackgroundGAB2 rs2373115 genotype increases the risk of Alzheimer’s (AD) and vascular (VD) diseases (Reiman et al., 2007; Lambert et al., 2013; Kondreddy et al., 2021). EEG reactivity to hyperventilation (HV) depends on hypocapnia‐induced cerebral vasoconstriction, which may be impaired in subjects with preclinical AD and VD. EEG differences in the carriers of GAB2 genotype in nondemented adults remain unknown. The study was aimed to determine the possible effect of GAB2 rs2373115 genotype on resting EEG and EEG reactivity to HV in non‐demented adults during aging.MethodThe enrolled cohort included 151 healthy volunteers, age range 20‐80 years, stratified by GAB2 rs2373115 genotype. Informed written consent was obtained from all participants. All subjects underwent a neurological examination and cognitive screening. The significance of the differences between the EEG in different subgroups was estimated using ANOVA in the general linear model. APOE and sex was included in the analysis as covariates.ResultIn the entire sample the presence of GAB2 C allele was associated with higher alpha2 relative power in resting EEG, with more pronounced differences in the right parietal area.EEG reactivity to HV decreased with aging, and the decrease was more pronounced in the carriers of GAB2 C allele. Under HV the older GAB2 AC&CC carriers as compared with the older GAB2 AA carriers had lower theta power. The HV reactivity of blood pressure and heart rate was decreased in aging to a greater extend in the GAB2 C allele carriers than in the homozygous GAB2 AA individuals.ConclusionThe results show that GAB2 genotype is associated with alpha2 relative power difference in non‐demented adults. Reduced EEG and vascular reactivity to HV in the older GAB2 C allele carriers indicates altered cerebrovascular reactivity to hypocapnia and suggests that vascular factors can mediate GAB2‐related AD susceptibility.The study was supported by Russian Science Foundation (Project N 22‐15‐00448, Project N 19‐75‐30039 genotyping) and the National Institutes of Health, United States (grant R01AG054712 to ER statistical analysis).