Liu Xiaocao, Zeng Qingze, Luo Xiao, Li Kaicheng, Hong Hui, Wang Shuyue, Guan Xiaojun, Wu Jingjing, Zhang Ruiting, Zhang Tianyi, Li Zheyu, Fu Yanv, Wang Tao, Wang Chao, Xu Xiaojun, Huang Peiyu, Zhang Minming
Department of Radiology, The 2nd Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Department of Neurology, The 2nd Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Front Aging Neurosci. 2021 Apr 29;13:591347. doi: 10.3389/fnagi.2021.591347. eCollection 2021.
Apolipoprotein E (APOE) ε2 is a protective genetic factor for Alzheimer's disease (AD). However, the potential interaction effects between the APOE ε2 allele and disease status on the intrinsic brain activity remain elusive.
We identified 73 healthy control (HC) with APOE ε3/ε3, 61 mild cognitive impairment (MCI) subjects with APOE ε3/ε3, 24 HC with APOE ε2/ε3, and 10 MCI subjects with APOE ε2/ε3 from the ADNI database. All subjects underwent a resting-state functional MRI and Fluoro-deoxy-glucose positron emission tomography (FDG-PET). We used a fractional amplitude of low-frequency fluctuation (fALFF) to explore the spontaneous brain activity. Based on the mixed-effects analysis, we explored the interaction effects between the APOE ε2 allele versus disease status on brain activity and metabolism in a voxel-wise fashion (GRF corrected, < 0.01), followed by two-sample -tests (Bonferroni corrected, < 0.05). We then investigated the relationship between the mean imaging metrics and cognitive abilities.
There are no significant differences in gender, age, or education among the four groups. The interaction effect on brain activity was located in the inferior parietal lobule (IPL). analysis showed that APOE ε2/ε3 MCI had an increased IPL fALFF than APOE ε3/ε3 MCI. Regarding the APOE ε2 allele effects, we found that ε2 carriers had a decreased fALFF in the transverse temporal gyrus than non-carriers. Also, FDG-PET results showed a lower SUVR of the frontal lobe in APOE ε2 carriers than non-carriers. Furthermore, fALFF of IPL was correlated with the visuospatial function ( = -0.16, < 0.05).
APOE ε2 carriers might have a better brain reservation when coping with AD-related pathologies.
载脂蛋白E（APOE）ε2是阿尔茨海默病（AD）的一种保护性遗传因素。然而，APOE ε2等位基因与疾病状态之间对大脑内在活动的潜在相互作用仍不清楚。
我们从ADNI数据库中确定了73名携带APOE ε3/ε3的健康对照（HC）、61名携带APOE ε3/ε3的轻度认知障碍（MCI）受试者、24名携带APOE ε2/ε3的HC以及10名携带APOE ε2/ε3的MCI受试者。所有受试者均接受了静息态功能磁共振成像和氟脱氧葡萄糖正电子发射断层扫描（FDG-PET）。我们使用低频波动分数（fALFF）来探索大脑的自发活动。基于混合效应分析，我们以体素为单位探讨了APOE ε2等位基因与疾病状态之间对大脑活动和代谢的相互作用（高斯随机场校正，<0.01），随后进行双样本检验（Bonferroni校正，<0.05）。然后，我们研究了平均成像指标与认知能力之间的关系。
四组在性别、年龄或教育程度上无显著差异。对大脑活动的相互作用效应位于顶下小叶（IPL）。分析表明，携带APOE ε2/ε3的MCI患者的IPL fALFF高于携带APOE ε3/ε3的MCI患者。关于APOE ε2等位基因的影响，我们发现ε2携带者的颞横回fALFF低于非携带者。此外，FDG-PET结果显示，APOE ε2携带者额叶的标准化摄取值比非携带者低。此外，IPL的fALFF与视觉空间功能相关（=-0.16，<0.05）。
APOE ε2携带者在应对AD相关病理时可能具有更好的大脑储备。
