An Na, Fu Yu, Shi Jie, Guo Han-Ning, Yang Zheng-Wu, Li Yong-Chao, Li Shan, Wang Yin, Yao Zhi-Jun, Hu Bin
School of Information Science and Engineering, Lanzhou University, Lanzhou, Gansu Province, China.
Gansu Provincial Key Laboratory of Wearable Computing, School of Information Science and Engineering, Lanzhou University, Lanzhou, China.
J Alzheimers Dis. 2021;80(3):1311-1327. doi: 10.3233/JAD-201162.
The volume loss of the hippocampus and amygdala in non-demented individuals has been reported to increase the risk of developing Alzheimer's disease (AD). Many neuroimaging genetics studies mainly focused on the individual effects of APOE and CLU on neuroimaging to understand their neural mechanisms, whereas their synergistic effects have been rarely studied.
To assess whether APOE and CLU have synergetic effects, we investigated the epistatic interaction and combined effects of the two genetic variants on morphological degeneration of hippocampus and amygdala in the non-demented elderly at baseline and 2-year follow-up.
Besides the widely-used volume indicator, the surface-based morphometry method was also adopted in this study to evaluate shape alterations.
Our results showed a synergistic effect of homozygosity for the CLU risk allele C in rs11136000 and APOEɛ4 on the hippocampal and amygdalar volumes during a 2-year follow-up. Moreover, the combined effects of APOEɛ4 and CLU C were stronger than either of the individual effects in the atrophy progress of the amygdala.
These findings indicate that brain morphological changes are caused by more than one gene variant, which may help us to better understand the complex endogenous mechanism of AD.
据报道，非痴呆个体中海马体和杏仁核的体积减小会增加患阿尔茨海默病（AD）的风险。许多神经影像学遗传学研究主要关注载脂蛋白E（APOE）和补体蛋白C1q/肿瘤坏死因子相关蛋白1（CLU）对神经影像学的个体影响，以了解其神经机制，而它们的协同作用很少被研究。
为了评估APOE和CLU是否具有协同作用，我们在基线和2年随访时研究了这两种基因变异在非痴呆老年人海马体和杏仁核形态退变中的上位性相互作用和联合效应。
除了广泛使用的体积指标外，本研究还采用基于表面的形态测量方法来评估形状改变。
我们的结果显示，在2年随访期间，rs11136000中CLU风险等位基因C的纯合性与APOEε4对海马体和杏仁核体积具有协同作用。此外，在杏仁核萎缩进展中，APOEε4和CLU C的联合效应比任何一个单独效应都更强。
这些发现表明，大脑形态变化是由多种基因变异引起的，这可能有助于我们更好地理解AD复杂的内在机制。
