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肌萎缩侧索硬化症中葡萄糖代谢协方差网络的破坏

Disrupted Glucose Metabolism Covariance Network in Amyotrophic Lateral Sclerosis.

作者信息

Jin Xin, Wang Xueying, Zheng Dingxin, Yuan Pubing, Li Jianyu, Qiu Ting, Zhang Huixiong, Chen Yifan, Zhang Jinfan, Wu Feifei, Liu Qing, Grecucci Alessandro, Zhang Yuanchao, Wang Junling, Yi Xiaoping, Palaniyappan Lena, Braden B Blair

机构信息

The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Lab for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, Sichuan, P. R. China.

School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, Sichuan, P. R. China.

出版信息

CNS Neurosci Ther. 2025 Jul;31(7):e70537. doi: 10.1111/cns.70537.

DOI:10.1111/cns.70537

PMID:40726139

Abstract

AIMS

This study aimed to characterize the topological changes in glucose metabolism covariance networks in amyotrophic lateral sclerosis (ALS).

METHODS

We assessed the interregional coordination of F-FDG-PET data to examine topological alterations in individualized glucose metabolism covariance networks in 127 ALS patients compared to 128 healthy controls (HC).

RESULTS

Compared to HC, ALS patients showed reduced small-worldness (lower normalized clustering coefficient, higher normalized characteristic path length) and decreased global and local efficiency, suggesting impaired global integration and local segregation. These network metrics correlated with disease progression and motor function. Regionally, altered degree centrality affected motor and default mode networks, and related to GABAa and mGluR5 receptor expression. Transcriptomic associations further linked these changes to immune function, synaptic signaling, and protein regulation. Bidirectional shifts in connectivity strength were observed, with both increased connectivity and disease progression independently predicting reduced survival.

CONCLUSION

Our findings may provide valuable biomarkers for monitoring the progression of ALS and suggest potential mechanistic pathways for the development of innovative therapeutic strategies for this disorder.

摘要

目的

本研究旨在描述肌萎缩侧索硬化症（ALS）患者葡萄糖代谢协方差网络的拓扑变化。

方法

我们评估了F-FDG-PET数据的区域间协调性，以检查127例ALS患者与128例健康对照（HC）个体葡萄糖代谢协方差网络中的拓扑改变。

结果

与HC相比，ALS患者表现出小世界特性降低（归一化聚类系数较低，归一化特征路径长度较高）以及全局和局部效率降低，提示全局整合和局部隔离受损。这些网络指标与疾病进展和运动功能相关。在区域上，改变的度中心性影响运动和默认模式网络，并与GABAa和mGluR5受体表达相关。转录组关联进一步将这些变化与免疫功能、突触信号传导和蛋白质调节联系起来。观察到连接强度的双向变化，连接性增加和疾病进展均独立预测生存率降低。