Abstract:

Microglia, as the resident innate immune cells of the central nervous system, play a pivotal role in both the onset and progression of Alzheimer's disease (AD). Emerging evidence has shown that metabolic reprogramming serves as a critical determinant of microglial functional states and exerts profound effects on AD pathogenesis. In this review, we systematically synthesize recent advances concerning microglial metabolic reprogramming in AD, with particular emphasis on the contributions and underlying mechanisms of glucose, lipid and amino acid metabolism. We further examine how key genetic risk factors including APOE and TREM2 genes drive metabolic perturbations and functional impairment in microglia. The therapeutic promise of targeting metabolic pathways, especially via metabolic modulators such as transient receptor potential vanilloid 1 (TRPV1) agonists, is also underscored. Moreover, we discuss prevailing challenges in the field, including limitations inherent in current disease models and the complexity arising from microglial heterogeneity. Finally, we propose that integrating multi-omics approaches with spatially resolved technologies may enable a more comprehensive dissection of metabolism-immune crosstalk in AD and open new avenues for designing combination therapeutic regimens.

Key words: Alzheimer disease, Microglia, Metabolism, Cellular reprogramming, Glucose, Lipids, Amino acids, Apolipoprotein E4, Review

摘要：

小胶质细胞是中枢神经系统固有免疫细胞，在阿尔茨海默病的发生发展过程中起重要作用，而小胶质细胞代谢重编程在调控其功能状态过程中发挥核心作用，对疾病进展具有重大影响。本文拟从小胶质细胞葡萄糖、脂质和氨基酸代谢重编程在阿尔茨海默病中的作用机制、APOE和TREM2基因等遗传风险因素影响、瞬时受体电位香草酸亚型1激动剂等靶向代谢重编程药物干预潜力，以及当前研究在模型构建、小胶质细胞异质性等方面面临的挑战等维度结合相关研究进展进行系统概述，并对未来融合多组学与空间解析技术开展代谢-免疫网络研究的可能性进行展望，提出联合疗法的构想。

关键词: 阿尔茨海默病, 小神经胶质细胞, 代谢, 细胞重新编程, 葡萄糖, 脂类, 氨基酸类, 载脂蛋白E4, 综述

CLC Number: 

• R741