Interactive effects of APOE and CHRNA4 on attention and white matter volume in healthy middle-aged and older adults
Interactive effects of APOE and CHRNA4 on attention and white matter volume in healthy middle-aged and older adults
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DOI：
10.3758/cabn.6.1.31
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发表时间：
2006-03-01
影响因子：
2.9
通讯作者：
Parasuraman, Raja
中科院分区：
文献类型：
--
作者：
Espeseth, Thomas;Greenwood, Pameia M.;Parasuraman, Raja
在这项研究中，我们在注意定向的背景下，研究了神经元修复机制的效率和胆碱能神经传递效率之间交互作用的年龄相关变化。此外，我们还探讨了白质体积变化作为神经元基础的可能性。对230例健康中老年人(53~454岁)和65~75岁老年人(65~75岁)进行了APOE和烟碱受体亚单位基因CHRNA4的基因分型。参与者被要求进行一项视觉空间注意任务，该任务涉及字母辨别和不同有效性的位置线索。在接受MRI扫描的一组参与者中，也研究了基因对脑白质体积的影响。APOE与CHRNA4相互作用，同时也是CHRNA4 77纯合子的APOE-epsilon 4携带者在无效的位置提示后反应时间(RT)不成比例地减慢。这种互动在中年参与者中比在老年参与者中更强。APOE-epsilon 4/CHRNA4 TT联合基因型个体在注意任务中表现出较低的白质体积和较慢的整体反应时的趋势。神经传递基因(CHRNA4)和易感基因(APOE)的相互作用表明，神经元修复机制的效率可能调节胆碱能系统影响注意功能。
In the present study, we investigated age-related changes in interactions between efficiency of neuronal repair mechanisms and efficiency of cholinergic neurotransmission in the context of attentional orienting. In addition, we explored white matter volume changes as possible neuronal underpinnings. A sample of 230 healthy middle-aged (53-454 years) and older (65-75 years) adults was genotyped for polymorphisms of APOE and CHRNA4, a nicotinic receptor subunit gene. Participants were administered a visuospatial attention task involving letter discrimination with location cues of varying validity. Genotype effects on white matter volume were also investigated in a subset of participants who received MRI scans. APOE interacted with CHRNA4, such that APOE-epsilon 4 carriers who were also CHRNA4 77 homozygotes showed disproportionately slowed reaction time (RT) following invalid location cues. The interaction was stronger in the middle-aged participants than in the older participants. There was also a trend for individuals with combined APOE-epsilon 4/CHRNA4 TT genotypes to show both lower white matter volume and slower overall RT on the attention task. The interaction of a neurotransmission gene (CHRNA4) and a susceptibility gene (APOE) suggests that the efficiency of neuronal repair mechanisms may modulate the cholinergic system to influence attentional function.