Impact of KIBRA Polymorphism on Memory Function and the Hippocampus in Older Adults
Impact of KIBRA Polymorphism on Memory Function and the Hippocampus in Older Adults
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DOI：
10.1038/npp.2015.203
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发表时间：
2016-02
影响因子：
7.6
通讯作者：
A. V. Witte;T. Köbe;Lucia Kerti;D. Rujescu;A. Flöel
中科院分区：
文献类型：
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作者：
A. V. Witte;T. Köbe;Lucia Kerti;D. Rujescu;A. Flöel
KIBRA基因（肾脏和大脑表达的蛋白质）内的单核苷酸多态性rs 17070145与记忆功能和相关大脑区域的变化相关。然而，以往的研究得出了相互矛盾的结果，这可能是由于不同的样本特征或任务特定的影响。因此，我们的目的是确定KIBRA基因型对学习和记忆形成的影响，以及海马及其子领域的体积，微结构完整性和功能连接（FC）在一个特征良好的健康老年人队列。对140名受试者（72名女性，年龄50-80岁）进行KIBRA基因分型，并使用听觉言语学习任务测试记忆力。此外，受试者在3 T下进行结构和静息状态功能磁共振成像。使用自动分割（FreeSurfer软件）描绘子野。微结构的完整性进行了测量，使用平均扩散率（MD）来自扩散张量图像。基于种子的分析用于评估海马的FC模式。KIBRA T等位基因携带者表现出更好的记忆表现的趋势，在海马体中显著更高的体积和部分更低的MD，表明更好的微观结构，与非T等位基因携带者相比，在角amnu（CA）2/3和CA 4/齿状回子字段（所有P <0.008，Bonferroni校正）。此外，T等位基因携带者在同步HC网络之外的左侧海马区表现出较低的FC。总而言之，我们可以首次证明，年龄较大的T等位基因携带者在海马子区域内表现出更大的体积和更好的微观结构，这些海马子区域与长时程增强和神经发生有关，这是记忆过程的关键特征。此外，T等位基因携带者表现出更有选择性的海马FC网络。
The single nucleotide polymorphism rs17070145 within the KIBRA gene (kidney and brain expressed protein) has been associated with variations in memory functions and related brain areas. However, previous studies yielded conflicting results, which might be due to divergent sample characteristics or task-specific effects. Therefore, we aimed to determine the impact of KIBRA genotype on learning and memory formation, and volume, microstructural integrity and functional connectivity (FC) of the hippocampus and its subfields in a well-characterized cohort of healthy older adults. One-hundred and forty subjects (72 women, age 50–80) were KIBRA genotyped and memory was tested using the Auditory Verbal Learning Task. Also, subjects underwent structural and resting-state functional magnetic resonance imaging at 3T. Subfields were delineated using automated segmentation (FreeSurfer software). Microstructural integrity was measured using mean diffusivity (MD) derived from diffusion tensor images. Seed-based analyses were used to assess FC patterns of the hippocampus. KIBRA T-allele carriers showed a trend for better memory performance, and in the hippocampus significantly higher volumes and partly lower MD, indicative for better microstructure, compared with non-T-allele carriers in the cornu ammonis (CA) 2/3 and CA4/dentate gyrus subfields (all P⩽ 0.008, Bonferroni corrected). Also, T-allele carriers exhibited lower FC of the left hippocampus with areas outside the synchronized HC network. In sum, we could show for the first time that older T-allele carriers exhibited larger volumes and better microstructure within those hippocampus subfields that are implicated in long-term potentiation and neurogenesis, key features of memory processes. Moreover, T-allele carriers showed a more selective FC network of the hippocampus.