Dataset Information

Genetic Association Between Alzheimer's Disease Risk Variant of the PICALM Gene and EEG Functional Connectivity in Non-demented Adults.

ABSTRACT: Genome wide association studies (GWAS) have identified and validated the association of the PICALM genotype with Alzheimer's disease (AD). The PICALM rs3851179 A allele is thought to have a protective effect, whereas the G allele appears to confer risk for AD. The influence of the PICALM genotype on brain functional connectivity in non-demented subjects remains largely unknown. We examined the association of the PICALM rs3851179 genotype with the characteristics of lagged linear connectivity (LLC) of resting EEG sources in 104 non-demented adults younger than 60 years of age. The EEG analysis was performed using exact low-resolution brain electromagnetic tomography (eLORETA) freeware (Pascual-Marqui et al., 2011). We found that the carriers of the A PICALM allele (PICALM AA and AG genotypes) had higher widespread interhemispheric LLC of alpha sources compared to the carriers of the GG PICALM allele. An exploratory correlation analysis showed a moderate positive association between the alpha LLC interhemispheric characteristics and the corpus callosum size and between the alpha interhemispheric LLC characteristics and the Luria word memory scores. These results suggest that the PICALM rs3851179 A allele provides protection against cognitive decline by facilitating neurophysiological reserve capacities in non-demented adults. In contrast, lower functional connectivity in carriers of the AD risk variant, PICALM GG, suggests early functional alterations in alpha rhythm networks.

SUBMITTER: Ponomareva N

PROVIDER: S-EPMC7177435 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Genetic Association Between Alzheimer's Disease Risk Variant of the PICALM Gene and EEG Functional Connectivity in Non-demented Adults.

Ponomareva Natalya N Andreeva Tatiana T Protasova Maria M Konovalov Rodion R Krotenkova Marina M Malina Daria D Mitrofanov Andrey A Fokin Vitaly V Illarioshkin Sergey S Rogaev Evgeny E

Frontiers in neuroscience 20200416

Genome wide association studies (GWAS) have identified and validated the association of the PICALM genotype with Alzheimer's disease (AD). The PICALM rs3851179 A allele is thought to have a protective effect, whereas the G allele appears to confer risk for AD. The influence of the PICALM genotype on brain functional connectivity in non-demented subjects remains largely unknown. We examined the association of the PICALM rs3851179 genotype with the charact ...[more]

PMID: 32372909

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Project description:BACKGROUND:Although numerous electroencephalogram (EEG) studies have described differences in functional connectivity in Alzheimer's disease (AD) compared to healthy subjects, there is no general consensus on the methodology of estimating functional connectivity in AD. Inconsistent results are reported due to multiple methodological factors such as diagnostic criteria, small sample sizes and the use of functional connectivity measures sensitive to volume conduction. We aimed to investigate the reproducibility of the disease-associated effects described by commonly used functional connectivity measures with respect to the amyloid, tau and neurodegeneration (A/T/N) criteria. METHODS:Eyes-closed task-free 21-channel EEG was used from patients with probable AD and subjective cognitive decline (SCD), to form two cohorts. Artefact-free epochs were visually selected and several functional connectivity measures (AEC(-c), coherence, imaginary coherence, PLV, PLI, wPLI) were estimated in five frequency bands. Functional connectivity was compared between diagnoses using AN(C)OVA models correcting for sex, age and, additionally, relative power of the frequency band. Another model predicted the Mini-Mental State Exam (MMSE) score of AD patients by functional connectivity estimates. The analysis was repeated in a subpopulation fulfilling the A/T/N criteria, after correction for influencing factors. The analyses were repeated in the second cohort. RESULTS:Two large cohorts were formed (SCD/AD; n =?197/214 and n =?202/196). Reproducible effects were found for the AEC-c in the alpha and beta frequency bands (p =?6.20 × 10-7, Cohen's d =?-?0.53; p =?5.78 × 10-4, d =?-?0.37) and PLI and wPLI in the theta band (p =?3.81 × 10-8, d =?0.59; p =?1.62 × 10-8, d =?0.60, respectively). Only effects of the AEC-c remained significant after statistical correction for the relative power of the selected bandwidth. In addition, alpha band AEC-c correlated with disease severity represented by MMSE score. CONCLUSION:The choice of functional connectivity measure and frequency band can have a large impact on the outcome of EEG studies in AD. Our results indicate that in the alpha and beta frequency bands, the effects measured by the AEC-c are reproducible and the most valid in terms of influencing factors, correlation with disease severity and preferable properties such as correction for volume conduction. Phase-based measures with correction for volume conduction, such as the PLI, showed reproducible effects in the theta frequency band.

Dataset Information

Genetic Association Between Alzheimer's Disease Risk Variant of the PICALM Gene and EEG Functional Connectivity in Non-demented Adults.

Publications

Genetic Association Between Alzheimer's Disease Risk Variant of the <i>PICALM</i> Gene and EEG Functional Connectivity in Non-demented Adults.

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