Center for Biomedical Imaging, University of Science and Technology of China, Hefei, Anhui 230026, China; Department of Electrical and Electronics Engineering, College of Science and Technology, University of Rwanda, Kigali, Rwanda.
Center for Biomedical Imaging, University of Science and Technology of China, Hefei, Anhui 230026, China.
J Neurol Sci. 2022 Nov 15;442:120435. doi: 10.1016/j.jns.2022.120435. Epub 2022 Sep 23.
While several studies have substantially revealed the influence of the apolipoprotein E4 genotype (APOE4) on the vulnerability of Alzheimer's disease (AD), there are still far fewer studies investigating whether and how APOE4, in the absence of the amyloid-β (Aβ), alters regional brain atrophy, cerebro-cerebellar connectivity and cognitive performance in AD patients.
We employed MRI and neuropsychological data from 234 old adults with AD dementia, including 143 APOE4-positive (with ε2/ε4, ε3/ε4, or ε4/ε4 alleles) and 91 APOE4-negative (with ε2/ε2, ε2/ε3 or ε3/ε3), to investigate the cerebro-cerebellar connectivity in three cerebro-cerebellar brain networks: default mode network, motor network and affective-limbic network. Amyloid PET images were used to evaluate individual Aβ burdens, later used as covariates. Regional volumetric and cortical thickness measures were quantified in both the cerebellum and the cerebrum using the cerebellum segmentation algorithm and Freesurfer5.3, respectively.
Our corrected functional connectivity (FC) results showed that APOE4 carriers (APOE4+) had lower FC within the cerebro-cerebellar motor network. In addition, significant group differences in regional cortical thickness were observed in the left Crus I, the right VIIB, left superior frontal, and right middle temporal gyri. Group differences in regional brain volumes were observed in the left lobule V and right parstriangularis. Furthermore, multiple linear regression analysis indicated that APOE4+ AD patients show greater episodic memory impairment.
Since amyloid-β, age, education, and gender were included as confounds in the statistical models, our findings suggest that APOE4 independently contributes to brain atrophy, disrupted FC, and associated memory declines in AD patients.
虽然多项研究已充分揭示载脂蛋白 E4 基因型（APOE4）对阿尔茨海默病（AD）易感性的影响，但目前研究 APOE4 在没有淀粉样蛋白-β（Aβ）的情况下如何改变 AD 患者的区域脑萎缩、脑-小脑连接和认知表现的研究仍少之又少。
我们使用了 234 名患有 AD 痴呆的老年患者的 MRI 和神经心理学数据，包括 143 名 APOE4 阳性（携带 ε2/ε4、ε3/ε4 或 ε4/ε4 等位基因）和 91 名 APOE4 阴性（携带 ε2/ε2、ε2/ε3 或 ε3/ε3），以研究三个脑-小脑脑网络中的脑-小脑连接：默认模式网络、运动网络和情感边缘网络。使用淀粉样蛋白 PET 图像评估个体的 Aβ负担，后将其作为协变量。使用小脑分割算法和 Freesurfer5.3 分别在小脑和大脑中量化了小脑和大脑的区域体积和皮质厚度测量值。
我们的校正功能连接（FC）结果表明，APOE4 携带者（APOE4+）在脑-小脑运动网络内的 FC 较低。此外，在左侧 Crus I、右侧 VIIB、左侧额上回和右侧颞中回观察到明显的组间皮质厚度差异。在左侧 V 叶和右侧 parstriangularis 观察到区域脑体积的组间差异。此外，多元线性回归分析表明，APOE4+AD 患者表现出更严重的情景记忆障碍。
由于在统计模型中包含了淀粉样蛋白-β、年龄、教育和性别作为混杂因素，我们的研究结果表明，APOE4 独立导致 AD 患者的脑萎缩、FC 中断和相关的记忆下降。
