Bridging Integrator 1 (BIN1) Genotype Effects on Working Memory, Hippocampal Volume, and Functional Connectivity in Young Healthy Individuals
Bridging Integrator 1 (BIN1) Genotype Effects on Working Memory, Hippocampal Volume, and Functional Connectivity in Young Healthy Individuals
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桥接积分器 1 (BIN1) 基因型对年轻健康个体的工作记忆、海马体积和功能连接的影响
DOI：
10.1038/npp.2015.30
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发表时间：
2015-06-01
影响因子：
7.6
通讯作者：
Jiang, Tianzi
中科院分区：
文献类型：
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作者：
Zhang, Xiaolong;Yu, Jin-Tai;Jiang, Tianzi
阿尔茨海默病(AD)是痴呆症最常见的形式，表现出相当程度的遗传性。桥接整合子1(BIN1)基因是继载脂蛋白E(APOE)之后的第二大AD危险基因。然而，已建立的遗传风险基因座BIN1 rs744373如何以及何时赋予晚发性AD风险仍有待确定。在这里，我们在大样本中国受试者中使用成像遗传学策略，我们发现rs744373风险等位基因的健康纯合子携带者表现出更差的高负荷工作记忆(WM)表现，更大的海马体体积，以及双侧海马和右侧背外侧前额叶皮质(DLPFC)之间的功能连接降低，这反映了患者记忆和连接障碍的临床证据。我们的发现表明，rs744373本身或连锁不平衡的变异可能为BIN1提供了一种神经遗传学机制，同时进一步验证了结合遗传和神经成像策略来监测AD风险个体的可能性。
Alzheimer's disease (AD) is the most common form of dementia and exhibits a considerable level of heritability. The bridging integrator 1 (BIN1) gene has recently been identified in several large genome-wide association studies (GWAS) as the second most important risk locus for AD following apolipoprotein E (APOE). However, how and when the established genetic risk locus BIN1 rs744373 confers risk to late-onset AD has yet to be determined. Here using an imaging genetic strategy in large-sample Chinese subjects, we show that healthy homozygous carriers of the rs744373 risk allele exhibit worse high-load working memory (WM) performance, larger hippocampal volume and lower functional connectivity between the bilateral hippocampus and the right dorsolateral prefrontal cortex (DLPFC), mirroring clinical evidence of disturbed memory and connectivity in patients. Our findings demonstrate that rs744373 itself or a variation in linkage disequilibrium may provide a neurogenetic mechanism for BIN1 while further validating the possibility of combining genetic and neuroimaging strategies to monitor individuals at risk for AD.