Impact of APOE and BDNF Val66Met Gene Polymorphisms on Cognitive Functions in Patients with Amnestic Mild Cognitive Impairment
Impact of APOE and BDNF Val66Met Gene Polymorphisms on Cognitive Functions in Patients with Amnestic Mild Cognitive Impairment
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DOI：
10.3233/jad-190464
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发表时间：
2020-01-01
影响因子：
4
通讯作者：
Hort, Jakub
中科院分区：
文献类型：
--
作者：
Cechova, Katerina;Andel, Ross;Hort, Jakub
载脂蛋白（APOE）β 4是晚发性阿尔茨海默病（AD）的一个众所周知的危险因素，但其他AD相关基因多态性也可能是重要的，如脑源性神经营养因子（BDNF）基因内的多态性。BDNF Val 66 Met的携带与认知正常的老年人中认知能力下降更快和大脑萎缩更严重有关。因此，我们研究了同时存在APOE和BDNF多态性对遗忘型轻度认知障碍（aMCI）患者认知功能和脑形态测量学的影响。从捷克脑老化研究中招募了107名aMCI患者（平均年龄= 72.2岁），根据APOE和BDNF基因多态性，将其分为4组：104（-）BDNF（瓦尔/瓦尔）（n = 37）、104（-）BDNF（Met）（n = 19）、104（+）BDNF（瓦尔/瓦尔）（n = 35）和104（+）BDNF（Met）（n = 16）。所有患者均接受了临床检查、磁共振成像和复杂神经心理电池检查。与其他多态性组相比，APOE β 4（+）和BDNF Met的组合与即时和延迟回忆的记忆表现显著较差相关。我们没有观察到在β 4（+）BDNF（Met）组中与记忆功能相关的区域萎缩增加。我们的研究结果表明，携带β 4（+）BDNF（Met）与更明显的记忆功能障碍有关，这是早期AD的典型特征，但与aMCI患者的脑结构变化无关。这些发现表明，在APOE β 4/BDNF Met携带者中，影响记忆的突触功能障碍可能先于明显的结构变化。
Apolipoprotein (APOE) epsilon 4 is a well-known risk factor for late-onset Alzheimer's disease (AD), but other AD-related gene polymorphisms might also be important, such as the polymorphism within the brain-derived neurotrophic factor (BDNF) gene. Carriage of BDNF Val66Met has been associated with faster cognitive decline and greater hippocamp al atrophy in cognitively normal elderly. Thus, we examined the effects of the concurrent presence of APOE and BDNF polymorphisms on cognitive functions and brain morphometry in amnestic mild cognitive impairment (aMCI) patients. 107 aMCI patients (mean age = 72.2) were recruited from the Czech Brain Aging Study and, based on APOE and BDNF genes polymorphisms, were divided into four groups: epsilon 4(-)BDNF(Val/Val) (n = 37), epsilon 4(-)BDNF(Met) (n = 19), epsilon 4(+)BDNF(Val/Val) (n = 35), and epsilon 4(+)BDNF(Met) (n = 16). All patients underwent clinical examination, magnetic resonance imaging, and complex neuropsychological battery. The combination of APOE epsilon 4(+) and BDNF Met was associated with significantly worse memory performance in immediate and delayed recall compared to other polymorphism groups. We did not observe increased atrophy in areas related to memory function in the epsilon 4(+)BDNF(Met) group. Our findings suggest that carriage of epsilon 4(+)BDNF(Met) is associated with more pronounced memory dysfunction, a typical feature of early AD, but not with structural brain changes in aMCI patients. These findings suggest that in APOE epsilon 4/BDNF Met carriers, synaptic dysfunction affecting memory may precede pronounced structural changes.