Cargando…
ABCA7 polymorphisms correlate with memory impairment and default mode network in patients with APOEε4-associated Alzheimer’s disease
BACKGROUND: Since both APOE and ABCA7 protein expression may independently reduce neuritic plaque burden and reorganize fibrillar amyloid burden-mediated disruption of functional connectivity in the default mode network, we aimed to investigate the effect of the APOE-ABCA7 interaction on default mod...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6909474/ https://www.ncbi.nlm.nih.gov/pubmed/31831047 http://dx.doi.org/10.1186/s13195-019-0563-3 |
_version_ | 1783478947751657472 |
---|---|
author | Chang, Ya-Ting Hsu, Shih-Wei Huang, Shu-Hua Huang, Chi-Wei Chang, Wen-Neng Lien, Chia-Yi Lee, Jun-Jun Lee, Chen-Chang Chang, Chiung-Chih |
author_facet | Chang, Ya-Ting Hsu, Shih-Wei Huang, Shu-Hua Huang, Chi-Wei Chang, Wen-Neng Lien, Chia-Yi Lee, Jun-Jun Lee, Chen-Chang Chang, Chiung-Chih |
author_sort | Chang, Ya-Ting |
collection | PubMed |
description | BACKGROUND: Since both APOE and ABCA7 protein expression may independently reduce neuritic plaque burden and reorganize fibrillar amyloid burden-mediated disruption of functional connectivity in the default mode network, we aimed to investigate the effect of the APOE-ABCA7 interaction on default mode network in Alzheimer’s disease. METHODS: Two hundred and eighty-seven individuals with a diagnosis of typical Alzheimer’s disease were included in this study. Memory was characterized and compared between APOE-ε4+ carriers and APOE-ε4 non-carriers within ABCA7 rs3764650T allele homozygous carriers and ABCA7 rs3764650G allele carriers, respectively. Two-way analysis of variance was used to identify a significant interaction effect between APOE (APOE-ε4+ carriers versus APOE-ε4 non-carriers) and ABCA7 (ABCA7 rs3764650T allele homozygous versus ABCA7 rs3764650G allele carriers) on memory scores and functional connectivity in each default mode network subsystem. RESULTS: In ABCA7 rs3764650G allele carriers, APOE-ε4+ carriers had lower memory scores (t (159) = − 4.879; P < 0.001) compared to APOE-ε4 non-carriers, but APOE-ε4+ carriers and APOE-ε4 non-carriers did not have differences in memory (P > 0.05) within ABCA7 rs3764650T allele homozygous carriers. There was a significant APOE-ABCA7 interaction effect on the memory (F3, 283 = 4.755, P = 0.030). In the default mode network anchored by the entorhinal seed, the peak neural activity of the cluster that was significantly associated with APOE-ABCA7 interaction effects (P = 0.00002) was correlated with the memory (ρ = 0.129, P = 0.030). CONCLUSIONS: Genetic-biological systems may impact disease presentation and therapy. Clarifying the effect of APOE-ABCA7 interactions on the default mode network and memory is critical to exploring the complex pathogenesis of Alzheimer’s disease and refining a potential therapy. |
format | Online Article Text |
id | pubmed-6909474 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-69094742019-12-19 ABCA7 polymorphisms correlate with memory impairment and default mode network in patients with APOEε4-associated Alzheimer’s disease Chang, Ya-Ting Hsu, Shih-Wei Huang, Shu-Hua Huang, Chi-Wei Chang, Wen-Neng Lien, Chia-Yi Lee, Jun-Jun Lee, Chen-Chang Chang, Chiung-Chih Alzheimers Res Ther Research BACKGROUND: Since both APOE and ABCA7 protein expression may independently reduce neuritic plaque burden and reorganize fibrillar amyloid burden-mediated disruption of functional connectivity in the default mode network, we aimed to investigate the effect of the APOE-ABCA7 interaction on default mode network in Alzheimer’s disease. METHODS: Two hundred and eighty-seven individuals with a diagnosis of typical Alzheimer’s disease were included in this study. Memory was characterized and compared between APOE-ε4+ carriers and APOE-ε4 non-carriers within ABCA7 rs3764650T allele homozygous carriers and ABCA7 rs3764650G allele carriers, respectively. Two-way analysis of variance was used to identify a significant interaction effect between APOE (APOE-ε4+ carriers versus APOE-ε4 non-carriers) and ABCA7 (ABCA7 rs3764650T allele homozygous versus ABCA7 rs3764650G allele carriers) on memory scores and functional connectivity in each default mode network subsystem. RESULTS: In ABCA7 rs3764650G allele carriers, APOE-ε4+ carriers had lower memory scores (t (159) = − 4.879; P < 0.001) compared to APOE-ε4 non-carriers, but APOE-ε4+ carriers and APOE-ε4 non-carriers did not have differences in memory (P > 0.05) within ABCA7 rs3764650T allele homozygous carriers. There was a significant APOE-ABCA7 interaction effect on the memory (F3, 283 = 4.755, P = 0.030). In the default mode network anchored by the entorhinal seed, the peak neural activity of the cluster that was significantly associated with APOE-ABCA7 interaction effects (P = 0.00002) was correlated with the memory (ρ = 0.129, P = 0.030). CONCLUSIONS: Genetic-biological systems may impact disease presentation and therapy. Clarifying the effect of APOE-ABCA7 interactions on the default mode network and memory is critical to exploring the complex pathogenesis of Alzheimer’s disease and refining a potential therapy. BioMed Central 2019-12-12 /pmc/articles/PMC6909474/ /pubmed/31831047 http://dx.doi.org/10.1186/s13195-019-0563-3 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Chang, Ya-Ting Hsu, Shih-Wei Huang, Shu-Hua Huang, Chi-Wei Chang, Wen-Neng Lien, Chia-Yi Lee, Jun-Jun Lee, Chen-Chang Chang, Chiung-Chih ABCA7 polymorphisms correlate with memory impairment and default mode network in patients with APOEε4-associated Alzheimer’s disease |
title | ABCA7 polymorphisms correlate with memory impairment and default mode network in patients with APOEε4-associated Alzheimer’s disease |
title_full | ABCA7 polymorphisms correlate with memory impairment and default mode network in patients with APOEε4-associated Alzheimer’s disease |
title_fullStr | ABCA7 polymorphisms correlate with memory impairment and default mode network in patients with APOEε4-associated Alzheimer’s disease |
title_full_unstemmed | ABCA7 polymorphisms correlate with memory impairment and default mode network in patients with APOEε4-associated Alzheimer’s disease |
title_short | ABCA7 polymorphisms correlate with memory impairment and default mode network in patients with APOEε4-associated Alzheimer’s disease |
title_sort | abca7 polymorphisms correlate with memory impairment and default mode network in patients with apoeε4-associated alzheimer’s disease |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6909474/ https://www.ncbi.nlm.nih.gov/pubmed/31831047 http://dx.doi.org/10.1186/s13195-019-0563-3 |
work_keys_str_mv | AT changyating abca7polymorphismscorrelatewithmemoryimpairmentanddefaultmodenetworkinpatientswithapoee4associatedalzheimersdisease AT hsushihwei abca7polymorphismscorrelatewithmemoryimpairmentanddefaultmodenetworkinpatientswithapoee4associatedalzheimersdisease AT huangshuhua abca7polymorphismscorrelatewithmemoryimpairmentanddefaultmodenetworkinpatientswithapoee4associatedalzheimersdisease AT huangchiwei abca7polymorphismscorrelatewithmemoryimpairmentanddefaultmodenetworkinpatientswithapoee4associatedalzheimersdisease AT changwenneng abca7polymorphismscorrelatewithmemoryimpairmentanddefaultmodenetworkinpatientswithapoee4associatedalzheimersdisease AT lienchiayi abca7polymorphismscorrelatewithmemoryimpairmentanddefaultmodenetworkinpatientswithapoee4associatedalzheimersdisease AT leejunjun abca7polymorphismscorrelatewithmemoryimpairmentanddefaultmodenetworkinpatientswithapoee4associatedalzheimersdisease AT leechenchang abca7polymorphismscorrelatewithmemoryimpairmentanddefaultmodenetworkinpatientswithapoee4associatedalzheimersdisease AT changchiungchih abca7polymorphismscorrelatewithmemoryimpairmentanddefaultmodenetworkinpatientswithapoee4associatedalzheimersdisease |