APOE genotype modulates proton magnetic resonance spectroscopy metabolites in the aging brain.
APOE genotype modulates proton magnetic resonance spectroscopy metabolites in the aging brain.
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DOI：
10.1016/j.biopsych.2013.05.022
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发表时间：
2014-05-01
影响因子：
10.6
通讯作者：
Goldberg, Terry E.
中科院分区：
文献类型：
--
作者：
Gomar, Jesus J.;Gordon, Marc L.;Dickinson, Dwight;Kingsley, Peter B.;Ulug, Aziz M.;Keehlisen, Lynda;Huet, Sarah;Buthorn, Justin J.;Koppel, Jeremy;Christen, Erica;Conejero-Goldberg, Concepcion;Davies, Peter;Goldberg, Terry E.
关键词：
质子磁共振波谱（1H-MRS）研究健康老龄化报告不一致的结果，并没有系统地考虑到可能的调节作用的载脂蛋白E基因型。我们的目的是量化健康受试者脑代谢物的变化与年龄和阿尔茨海默病的APOE E4遗传风险因素的存在。此外，我们还研究了这些措施与认知的关系。我们研究了112名年龄在50岁至86岁之间的正常成年人，他们进行了载脂蛋白E遗传多态性的基因分型。在后扣带回和楔前叶区域获得1H-MRS代谢产物的测量值。一般认知功能，记忆，执行功能，语义流畅性和处理速度的措施也得到了。一般线性模型分析表明，老年APOE E4携带者有显着较高的胆碱/肌酸和肌醇/肌酸比APOE E3纯合子。结构方程建模得到了一个具有极好拟合优度的模型，其中APOE ×年龄相互作用和APOE状态均对1H-MRS代谢物（胆碱/肌酸和肌醇/肌酸）有显著影响。此外，1H-MRS代谢产物介导了APOE ×年龄变量对认知的调节。在健康老龄化的正常人群中，胆碱/肌酸和肌醇/肌酸比值在APOE E4携带者中显著增加，表明老年携带者存在神经炎症过程和更大的膜周转。结构方程模型分析证实了这些可能的神经退行性标志物，也表明了这些代谢产物对老年APOE E4携带者认知能力的介导作用。
Proton magnetic resonance spectroscopy (1H-MRS) studies on healthy aging have reported inconsistent findings and have not systematically taken into account the possible modulatory effect of APOE genotype. We aimed to quantify brain metabolite changes in healthy subjects in relation to age and the presence of the APOE E4 genetic risk factor for Alzheimer's disease. Additionally, we examined these measures in relation to cognition. We studied a cohort of 112 normal adults between 50 and 86 years old who were genotyped for APOE genetic polymorphism. Measurements of 1H-MRS metabolites were obtained in the posterior cingulate and precuneus region. Measures of general cognitive functioning, memory, executive function, semantic fluency, and speed of processing were also obtained. General linear model analysis demonstrated that older APOE E4 carriers had significantly higher choline/creatine and myoinositol/creatine ratios than APOE E3 homozygotes. Structural equation modeling resulted in a model with an excellent goodness of fit and in which the APOE × age interaction and APOE status each had a significant effect on 1H-MRS metabolites (choline/creatine and myo-inositol/creatine). Furthermore, the APOE × age variable modulation of cognition was mediated by 1H-MRS metabolites. In a healthy aging normal population, choline/creatine and myo-inositol/creatine ratios were significantly increased in APOE E4 carriers, suggesting the presence of neuroinflammatory processes and greater membrane turnover in older carriers. Structural equation modeling analysis confirmed these possible neurodegenerative markers and also indicated the mediator role of these metabolites on cognitive performance among older APOE E4 carriers.
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影响因子：
2.6
作者：
Kantarci, K.
通讯作者：
Kantarci, K.
影响因子：
168.9
作者：
Cagnin, A;Brooks, DJ;Banati, RB
通讯作者：
Banati, RB
DOI：
10.1073/pnas.0812697106
发表时间：
2009-02-10
影响因子：
11.1
作者：
Agosta, Federica;Vossel, Keith A.;Gorno-Tempini, Maria Luisa
通讯作者：
Gorno-Tempini, Maria Luisa
DOI：
10.1073/pnas.0308627101
发表时间：
2004-03-30
影响因子：
11.1
作者：
Greicius, MD;Srivastava, G;Menon, V
通讯作者：
Menon, V
影响因子：
9.9
作者：
Benarroch, Eduardo E.
通讯作者：
Benarroch, Eduardo E.