Department of Psychiatry, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
Department of Psychiatry, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
Int J Mol Sci. 2023 Jul 8;24(14):11250. doi: 10.3390/ijms241411250.
The ε2 allele of apolipoprotein E (ε2) has neuroprotective effects against beta-amyloid (Aβ) pathology in Alzheimer's disease (AD). However, its impact on the functional connectivity and hub efficiency in cognitively normal older adults (CN) with ε2 is unclear. We investigated the functional connectivity differences in the default mode network (DMN), salience network, and central executive network (CEN) between A-PET-negative (N = 29) and A-PET-positive (N = 15) CNs with ε2/ε2 or ε2/ε3 genotypes. The A-PET-positive CNs exhibited a lower anterior DMN functional connectivity, higher posterior DMN functional connectivity, and increased CEN functional connectivity compared to the A-PET-negative CNs. Cerebral Aβ retention was negatively correlated with anterior DMN functional connectivity and positively correlated with posterior DMN and anterior CEN functional connectivity. A graph theory analysis showed that the A-PET-positive CNs displayed a higher betweenness centrality in the middle frontal gyrus (left) and medial fronto-parietal regions (left). The betweenness centrality in the middle frontal gyrus (left) was positively correlated with Aβ retention. Our findings reveal a reversed anterior-posterior dissociation in the DMN functional connectivity and heightened CEN functional connectivity in A-PET-positive CNs with ε2. Hub efficiencies, measured by betweenness centrality, were increased in the DMN and CEN of the A-PET-positive CNs with ε2. These results suggest unique functional connectivity responses to Aβ pathology in CN individuals with ε2.
载脂蛋白 E（ApoE）ε2 等位基因对阿尔茨海默病（AD）β-淀粉样蛋白（Aβ）病理学具有神经保护作用。然而，其对携带 ε2 的认知正常老年人（CN）中默认模式网络（DMN）、突显网络和中央执行网络（CEN）的功能连接和枢纽效率的影响尚不清楚。我们研究了具有 ε2/ε2 或 ε2/ε3 基因型的 A-PET 阴性（N=29）和 A-PET 阳性（N=15）CN 之间 DMN、突显网络和 CEN 之间的功能连接差异。与 A-PET 阴性 CN 相比，A-PET 阳性 CN 表现出更低的前 DMN 功能连接、更高的后 DMN 功能连接和增加的 CEN 功能连接。大脑 Aβ 保留与前 DMN 功能连接呈负相关，与后 DMN 和前 CEN 功能连接呈正相关。图论分析表明，A-PET 阳性 CN 在中额回（左）和内侧额顶叶区域（左）中表现出更高的介数中心度。中额回（左）的介数中心度与 Aβ 保留呈正相关。我们的研究结果揭示了携带 ε2 的 A-PET 阳性 CN 中 DMN 功能连接的反向前-后分离和 CEN 功能连接的增强。通过介数中心度测量的枢纽效率在 A-PET 阳性 CN 的 DMN 和 CEN 中增加。这些结果表明，携带 ε2 的 CN 个体对 Aβ 病理学具有独特的功能连接反应。
