Jin Suhui, Wang Jinhui, He Yong
Institute for Brain Research and Rehabilitation, Guangzhou 510631, China.
Guangdong Key Laboratory of Mental Health and Cognitive Science, Guangzhou 510631, China.
Biophys Rep. 2024 Aug 31;10(4):213-229. doi: 10.52601/bpr.2024.230025.
Alzheimer's disease (AD) has been conceptualized as a syndrome of brain network dysfunction. Recent imaging connectomics studies have provided unprecedented opportunities to map structural and functional brain networks in AD. By reviewing molecular, imaging, and computational modeling studies, we have shown that highly connected brain hubs are primarily distributed in the medial and lateral prefrontal, parietal, and temporal regions in healthy individuals and that the hubs are selectively and severely affected in AD as manifested by increased amyloid-beta deposition and regional atrophy, hypo-metabolism, and connectivity dysfunction. Furthermore, AD-related hub degeneration depends on the imaging modality with the most notable degeneration in the medial temporal hubs for morphological covariance networks, the prefrontal hubs for structural white matter networks, and in the medial parietal hubs for functional networks. Finally, the AD-related hub degeneration shows metabolic, molecular, and genetic correlates. Collectively, we conclude that the brain-network-hub-degeneration framework is promising to elucidate the biological mechanisms of network dysfunction in AD, which provides valuable information on potential diagnostic biomarkers and promising therapeutic targets for the disease.
阿尔茨海默病（AD）已被概念化为一种脑网络功能障碍综合征。最近的成像连接组学研究为绘制AD患者的脑结构和功能网络提供了前所未有的机会。通过回顾分子、成像和计算建模研究，我们发现，在健康个体中，高度连接的脑枢纽主要分布在内侧和外侧前额叶、顶叶和颞叶区域，并且在AD中，这些枢纽会受到选择性且严重的影响，表现为淀粉样β沉积增加、区域萎缩、代谢减退和连接功能障碍。此外，与AD相关的枢纽退化取决于成像方式，内侧颞叶枢纽在形态协方差网络中退化最为明显，前额叶枢纽在结构白质网络中退化最为明显，而在内侧顶叶枢纽在功能网络中退化最为明显。最后，与AD相关的枢纽退化表现出代谢、分子和遗传相关性。总体而言，我们得出结论，脑网络枢纽退化框架有望阐明AD中网络功能障碍的生物学机制，这为该疾病的潜在诊断生物标志物和有前景的治疗靶点提供了有价值的信息。
