APOE-MS4A genetic interactions are associated with executive dysfunction and network abnormality in clinically mild Alzheimer's disease
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) wit...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-01-01
|
| Series: | NeuroImage: Clinical |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213158218303693 |
| _version_ | 1811289113454706688 |
|---|---|
| author | Ya-Ting Chang Etsuro Mori Maki Suzuki Manabu Ikeda Chi-Wei Huang Jun-Jun Lee Wen-Neng Chang Chiung-Chih Chang |
| author_facet | Ya-Ting Chang Etsuro Mori Maki Suzuki Manabu Ikeda Chi-Wei Huang Jun-Jun Lee Wen-Neng Chang Chiung-Chih Chang |
| author_sort | Ya-Ting Chang |
| collection | DOAJ |
| description | 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. Keywords: APOE, Calculation, Executive control network, Genetic interaction, MS4A |
| first_indexed | 2024-04-13T03:49:14Z |
| format | Article |
| id | doaj.art-8017c9f390304a789af7c362779ee2e9 |
| institution | Directory Open Access Journal |
| issn | 2213-1582 |
| language | English |
| last_indexed | 2024-04-13T03:49:14Z |
| publishDate | 2019-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | NeuroImage: Clinical |
| spelling | doaj.art-8017c9f390304a789af7c362779ee2e92022-12-22T03:03:53ZengElsevierNeuroImage: Clinical2213-15822019-01-0121APOE-MS4A genetic interactions are associated with executive dysfunction and network abnormality in clinically mild Alzheimer's diseaseYa-Ting Chang0Etsuro Mori1Maki Suzuki2Manabu Ikeda3Chi-Wei Huang4Jun-Jun Lee5Wen-Neng Chang6Chiung-Chih Chang7Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan; Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, JapanDepartment of Behavioral Neurology and Neuropsychiatry, Osaka University United Graduate School of Child Development, Suita, Osaka, JapanDepartment of Behavioral Neurology and Neuropsychiatry, Osaka University United Graduate School of Child Development, Suita, Osaka, JapanDepartment of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, JapanDepartment of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, TaiwanDepartment of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, TaiwanDepartment of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, TaiwanDepartment of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan; Corresponding author at: Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, 123, Ta-Pei Road, Niaosung, Kaohsiung 833, Taiwan.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. Keywords: APOE, Calculation, Executive control network, Genetic interaction, MS4Ahttp://www.sciencedirect.com/science/article/pii/S2213158218303693 |
| spellingShingle | Ya-Ting Chang Etsuro Mori Maki Suzuki Manabu Ikeda Chi-Wei Huang Jun-Jun Lee Wen-Neng Chang Chiung-Chih Chang APOE-MS4A genetic interactions are associated with executive dysfunction and network abnormality in clinically mild Alzheimer's disease NeuroImage: Clinical |
| title | APOE-MS4A genetic interactions are associated with executive dysfunction and network abnormality in clinically mild Alzheimer's disease |
| title_full | APOE-MS4A genetic interactions are associated with executive dysfunction and network abnormality in clinically mild Alzheimer's disease |
| title_fullStr | APOE-MS4A genetic interactions are associated with executive dysfunction and network abnormality in clinically mild Alzheimer's disease |
| title_full_unstemmed | APOE-MS4A genetic interactions are associated with executive dysfunction and network abnormality in clinically mild Alzheimer's disease |
| title_short | APOE-MS4A genetic interactions are associated with executive dysfunction and network abnormality in clinically mild Alzheimer's disease |
| title_sort | apoe ms4a genetic interactions are associated with executive dysfunction and network abnormality in clinically mild alzheimer s disease |
| url | http://www.sciencedirect.com/science/article/pii/S2213158218303693 |
| work_keys_str_mv | AT yatingchang apoems4ageneticinteractionsareassociatedwithexecutivedysfunctionandnetworkabnormalityinclinicallymildalzheimersdisease AT etsuromori apoems4ageneticinteractionsareassociatedwithexecutivedysfunctionandnetworkabnormalityinclinicallymildalzheimersdisease AT makisuzuki apoems4ageneticinteractionsareassociatedwithexecutivedysfunctionandnetworkabnormalityinclinicallymildalzheimersdisease AT manabuikeda apoems4ageneticinteractionsareassociatedwithexecutivedysfunctionandnetworkabnormalityinclinicallymildalzheimersdisease AT chiweihuang apoems4ageneticinteractionsareassociatedwithexecutivedysfunctionandnetworkabnormalityinclinicallymildalzheimersdisease AT junjunlee apoems4ageneticinteractionsareassociatedwithexecutivedysfunctionandnetworkabnormalityinclinicallymildalzheimersdisease AT wennengchang apoems4ageneticinteractionsareassociatedwithexecutivedysfunctionandnetworkabnormalityinclinicallymildalzheimersdisease AT chiungchihchang apoems4ageneticinteractionsareassociatedwithexecutivedysfunctionandnetworkabnormalityinclinicallymildalzheimersdisease |