Department of Radiology, Qilu Hospital of Shangdong University, China.
Department of Neurology, Qilu Hospital of Shangdong University, China.
J Gerontol A Biol Sci Med Sci. 2019 Oct 4;74(11):1725-1733. doi: 10.1093/gerona/glz004.
Genetic factors play a critical role in the development of Alzheimer's disease (AD). Kidney and brain expressed protein (KIBRA) and apolipoprotein E (APOE) are involved in episodic memory performance and AD. However, the interactions between KIBRA and APOE on brain functional network connectivity (FNC) remain unknown in healthy older people. Using independent component analysis, we systematically investigated additive and epistatic interactions of KIBRA rs1707045 and APOE on FNC in 170 healthy older Chinese people of Han ethnicity. We found significant additive KIBRA-APOE interactions on brain FNC in the right medial prefrontal cortex, the posterior cingulate cortex in the default-mode network, and the dorsal anterior cingulate cortex in the salience network. We also found significant epistatic KIBRA-APOE interactions on brain FNC in the left superior frontal gyrus and left angular gyrus in default-mode network. No significant KIBRA-APOE interactions were detected in other brain resting-state networks. These findings suggest that healthy older people have additive and epistatic interactions of KIBRA and APOE gene variants, which modulate brain FNC and may partly elucidate their association with episodic memory performance and AD.
遗传因素在阿尔茨海默病（AD）的发展中起着关键作用。肾脏和脑表达蛋白（KIBRA）和载脂蛋白 E（APOE）参与情景记忆表现和 AD。然而，在健康老年人中，KIBRA 和 APOE 之间的相互作用对大脑功能网络连接（FNC）的影响尚不清楚。本研究采用独立成分分析，系统研究了 170 名汉族健康老年人中 KIBRA rs1707045 和 APOE 对 FNC 的加性和上位性相互作用。结果发现，在右侧内侧前额叶皮质、默认模式网络中的后扣带回皮质和突显网络中的背侧前扣带皮质中，KIBRA-APOE 存在显著的加性相互作用。在默认模式网络中的左侧额上回和左侧角回中，KIBRA-APOE 也存在显著的上位性相互作用。在其他大脑静息态网络中未发现 KIBRA-APOE 的相互作用。这些发现表明，健康老年人的 KIBRA 和 APOE 基因变异存在加性和上位性相互作用，调节大脑 FNC，并可能部分阐明其与情景记忆表现和 AD 的关联。
