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

Ponomareva, Natalya V
Andreeva, Tatiana V
Protasova, Maria S
Kunizheva, Svetlana S
Kuznetsova, Irina L
Kolesnikova, Ekaterina P
Malina, Daria D
Mitrofanov, Andrey A
Fokin, Vitaly F
Illarioshkin, Sergey N
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Abstract

The clusterin (CLU) rs11136000 CC genotype is a probable risk factor for Alzheimer's disease (AD). CLU, also known as the apolipoprotein J gene, shares certain properties with the apolipoprotein E (APOE) gene with a well-established relationship with AD. This study aimed to determine whether the electrophysiological patterns of brain activation during the letter fluency task (LFT) depend on CLU genotypes in adults without dementia. Previous studies have shown that LFT performance involves activation of the frontal cortex. We examined EEG alpha1 and alpha2 band desynchronization in the frontal regions during the LFT in 94 nondemented individuals stratified by CLU (rs11136000) genotype. Starting at 30 years of age, CLU CC carriers exhibited more pronounced task-related alpha2 desynchronization than CLU CT&TT carriers in the absence of any differences in LFT performance. In CLU CC carriers, alpha2 desynchronization was significantly correlated with age. Increased task-related activation in individuals at genetic risk for AD may reflect greater "effort" to perform the task and/or neuronal hyperexcitability. The results show that the CLU genotype is associated with neuronal hyperactivation in the frontal cortex during cognitive tasks performances in nondemented individuals, suggesting systematic vulnerability of LFT related cognitive networks in people carrying unfavorable CLU alleles.

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Ponomareva NV, Andreeva TV, Protasova MS, Kunizheva SS, Kuznetsova IL, Kolesnikova EP, Malina DD, Mitrofanov AA, Fokin VF, Illarioshkin SN, Rogaev EI. Neuronal Hyperactivation in EEG Data during Cognitive Tasks Is Related to the Apolipoprotein J/Clusterin Genotype in Nondemented Adults. Int J Mol Sci. 2023 Apr 5;24(7):6790. doi: 10.3390/ijms24076790. PMID: 37047762; PMCID: PMC10095572.

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10.3390/ijms24076790
PubMed ID
37047762
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Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).Attribution 4.0 International