载脂蛋白 Eε4 相关阿尔茨海默病患者的 ABCA7 多态性与记忆障碍和默认模式网络相关。
ABCA7 polymorphisms correlate with memory impairment and default mode network in patients with APOEε4-associated Alzheimer's disease.
机构信息
Department of Neurology, Institute of translational research in biomedicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123, Ta-Pei Road, Niaosung, Kaohsiung, 833, Taiwan.
Department of Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123, Ta-Pei Road, Niaosung, Kaohsiung, 833, Taiwan.
出版信息
Alzheimers Res Ther. 2019 Dec 12;11(1):103. doi: 10.1186/s13195-019-0563-3.
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.
背景
载脂蛋白 E（APOE）和 ABCA7 蛋白的表达都可能独立降低神经纤维缠结负担，并重新组织纤维状淀粉样物质负担介导的默认模式网络功能连接的中断，因此，我们旨在研究 APOE-ABCA7 相互作用对阿尔茨海默病患者默认模式网络的影响。
方法
本研究纳入了 287 名被诊断为典型阿尔茨海默病的患者。在 ABCA7 rs3764650T 等位基因纯合子携带者和 ABCA7 rs3764650G 等位基因携带者中，根据 APOE-ε4+ 载脂蛋白的携带情况，对记忆特征进行了比较，并在 ABCA7 rs3764650T 等位基因纯合子携带者和 ABCA7 rs3764650G 等位基因携带者中分别比较了 APOE-ε4+ 载脂蛋白和 APOE-ε4 非载脂蛋白携带者之间的记忆评分。采用双向方差分析来识别 APOE（APOE-ε4+ 载脂蛋白携带者与 APOE-ε4 非载脂蛋白携带者）和 ABCA7（ABCA7 rs3764650T 等位基因纯合子与 ABCA7 rs3764650G 等位基因携带者）在每个默认模式网络子系统中对记忆评分和功能连接的显著交互作用。
结果
在 ABCA7 rs3764650G 等位基因携带者中，APOE-ε4+ 载脂蛋白携带者的记忆评分低于 APOE-ε4 非载脂蛋白携带者（t（159）=-4.879；P<0.001），但 APOE-ε4 载脂蛋白携带者和 APOE-ε4 非载脂蛋白携带者在 ABCA7 rs3764650T 等位基因纯合子携带者中没有差异（P>0.05）。APOE-ABCA7 交互作用对记忆有显著影响（F3, 283=4.755，P=0.030）。在以内侧颞叶种子为中心的默认模式网络中，与 APOE-ABCA7 相互作用效应显著相关的聚类的峰值神经活动（P=0.00002）与记忆相关（ρ=0.129，P=0.030）。
结论
遗传-生物学系统可能会影响疾病的表现和治疗。阐明 APOE-ABCA7 相互作用对默认模式网络和记忆的影响，对于探索阿尔茨海默病的复杂发病机制和完善潜在的治疗方法至关重要。
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