不同脑区胰岛素抵抗在阿尔茨海默病中的作用

doi:10.3969/j.issn.1003-9198.2025.11.018

摘要/Abstract

摘要： 胰岛素抵抗在中枢神经系统的区域特异性作用日益受到关注。本综述系统整合近年研究发现,海马体、前额叶皮层及下丘脑等胰岛素高敏感性脑区在胰岛素抵抗状态下,可触发脑葡萄糖代谢紊乱、线粒体功能障碍、神经炎症级联放大、β-淀粉样蛋白异常沉积及Tau蛋白过度磷酸化等关键AD病理进程。其核心机制涉及胰岛素抵抗对脑区特异性胰岛素信号通路的破坏,进而导致突触可塑性损伤、神经营养支持减弱及神经元退行性变加速。值得注意的是,靶向干预策略在临床前研究中展现出调节AD病理的潜力。本文从不同脑区对胰岛素抵抗的敏感性出发,探讨其在AD中的作用机制,以期为AD的预防与治疗提供新的视角。

关键词: 脑区, 胰岛素抵抗, 阿尔茨海默病

Abstract: The region specific role of insulin resistance in the central nervous system is receiving increasing attention. This review systematically integrates recent research and finds that insulin sensitive brain regions such as the hippocampus, prefrontal cortex, and hypothalamus can trigger key pathological processes of Alzheimer’s disease, including glucose metabolism disorders, mitochondrial dysfunction, neuroinflammation cascade amplification, abnormal deposition of β-amyloid protein, and excessive phosphorylation of Tau protein, under insulin resistance. The core mechanism involves the disruption of brain region specific insulin signaling pathways by insulin resistance, leading to synaptic plasticity damage, weakened neurotrophic support, and accelerated neuronal degeneration. Notably, targeted intervention strategies have shown potential to modulate Alzheimer’s disease pathology in preclinical studies. Starting from the sensitivity of different brain regions to insulin resistance, this article explores its mechanism in Alzheimer’s disease, in order to provide a new perspective for the prevention and treatment of Alzheimer’s disease.

Key words: brain regions, insulin resistance, Alzheimer’s disease

中图分类号:

R 749.16

陈鹏瑶, 赵紫薇, 詹向红, 刘永. 不同脑区胰岛素抵抗在阿尔茨海默病中的作用[J]. 实用老年医学, 2025, 39(11): 1163-1168.

CHEN Pengyao, ZHAO Ziwei, ZHAN Xianghong, LIU Yong. Role of insulin resistance in different brain regions in Alzheimer’s disease[J]. Practical Geriatrics, 2025, 39(11): 1163-1168.

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