Dataset Information

APOE-MS4A genetic interactions are associated with executive dysfunction and network abnormality in clinically mild Alzheimer's disease.

ABSTRACT:

Purpose of the research

Although single nucleotide polymorphisms of membrane-spanning 4A (MS4A) (rs670139) and several other susceptibility genes have shown interaction effects on the risk of Alzheimer's disease (AD), little is known about the interaction effects of apolipoprotein E (APOE) with MS4A (rs670139) on cognitive performances, and the underlying pathogenesis is unclear. The study aimed to investigate the APOE-MS4A (rs670139) interaction effects on cognitive performances, cortical volumes, and functional connectivity (FC) in brain networks.

Principal results

Cognitive performances were characterized in each genotypic group, and were compared between normal controls and patients in each genotypic group. APOE-MS4A interaction effects on memory and executive function scores, cortical volumes, and FC in brain networks were demonstrated. Significant effects of APOE-MS4A interactions on FC were observed in executive control network (ECN) (T maxima = 4.99, false discovery rate-corrected p < .001), the calculation score (F3, 87 = 6.218; p = .015), and the volume in prefrontal (F3, 87 = 4.374; p = .039) and orbitofrontal cortices (F3, 87 = 6.022; p = .016). The calculation score was correlated with each frontal volume (cc) (ρ = 0.304; p = .004) and genetic interaction-associated FC in ECN (ρ = 0.282; p = .008). Variations in genotypes affected the relationship between the calculation score and each frontal volume (cc).

Major conclusions

These findings indicate that the genetic interaction effects on FC in ECN might contribute to pathogenic mechanisms underlying the interaction effects of APOE-MS4A on calculation ability in AD.

SUBMITTER: Chang YT

PROVIDER: S-EPMC6411654 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

APOE-MS4A genetic interactions are associated with executive dysfunction and network abnormality in clinically mild Alzheimer's disease.

Chang Ya-Ting YT Mori Etsuro E Suzuki Maki M Ikeda Manabu M Huang Chi-Wei CW Lee Jun-Jun JJ Chang Wen-Neng WN Chang Chiung-Chih CC

NeuroImage. Clinical 20181204

<h4>Purpose of the research</h4>Although single nucleotide polymorphisms of membrane-spanning 4A (MS4A) (rs670139) and several other susceptibility genes have shown interaction effects on the risk of Alzheimer's disease (AD), little is known about the interaction effects of apolipoprotein E (APOE) with MS4A (rs670139) on cognitive performances, and the underlying pathogenesis is unclear. The study aimed to investigate the APOE-MS4A (rs670139) interaction effects on cognitive performances, cortic ...[more]

PMID: 30528368

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Dataset Information

APOE-MS4A genetic interactions are associated with executive dysfunction and network abnormality in clinically mild Alzheimer's disease.

Purpose of the research

Principal results

Major conclusions

Publications

APOE-MS4A genetic interactions are associated with executive dysfunction and network abnormality in clinically mild Alzheimer's disease.

Similar Datasets

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