摘要
阿尔茨海默病(Alzheimer’s disease,AD)是一种以进行性认知功能障碍为核心表现的神经退行性疾病,其机制涉及β-淀粉样蛋白沉积、磷酸化tau蛋白聚集以及神经炎症等多重因素。β-羟丁酸(β-hydroxybutyrate,BHB)是体内的主要酮体,不仅可作为替代能源缓解神经元能量危机,还通过多靶点机制干预AD核心病理进程。本文从线粒体功能障碍、病理蛋白沉积、神经炎症、氧化应激胰岛素抵抗等关键病理机制入手,系统综述了BHB在AD中的神经保护机制。临床研究显示,BHB对APOEε4阴性患者认知改善显著,但现有内源性酮症诱导或外源性酮体补充策略仍存在诸多挑战。未来需优化BHB给药方案,明确有效血BHB浓度窗,推动其成为AD代谢干预的精准治疗选择。本综述为理解BHB在AD中的多机制协同作用及临床转化提供了理论框架。
Alzheimer's disease(AD)is a neurodegenerative disorder marked by progressive cognitive decline and driven by complex pathological processes,includingβ-amyloid deposition,hyperphosphorylated tau aggre gation,and neuroinflammation.β-Hydroxybutyrate(BHB),the predominant circulating ketone body,functions not only as an alternative energy substrate to mitigate neuronal energy deficits but also acts on multiple patholog ical targets central to AD progression.This review systematically summarizes the neuroprotective mechanisms of BHB in AD,focusing on mitochondrial dysfunction,pathological protein deposition,neuroinflammation,oxi dative stress,and insulin resistance.Clinical studies indicate that BHB significantly improves cognition in APOE e4-negative patients,yet current strategies for inducing endogenous ketosis or supplementing exogenous ketones face substantial challenges.Future research should focus on optimizing BHBadministration protocols,defining the optimal therapeutic blood concentration range,and advancing BHB as a targeted metabolic intervention for AD.Collectively,this review provides a theoretical framework for understanding the multi-mechanistic synergy of BHB in AD and its clinical translation.
作者
王路瑶
詹紫格
郑凯
WANG Luyao;ZHAN Zige;ZHENG Kai(Department of Geriatrics,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China;Key Laboratory of Vascular Aging,Ministry of Education,Wuhan 430030,China)
出处
《神经损伤与功能重建》
2025年第12期737-741,共5页
Neural Injury and Functional Reconstruction
基金
国家自然科学基金项目(丰富环境通过DNA甲基化调控Foxd3/miR-135a-5p通路改善AD小鼠学习记忆的机制研究,No.82371442)。
关键词
阿尔茨海默病
Β-羟丁酸
线粒体功能障碍
病理蛋白
神经炎症
Alzheimer’s disease
β-hydroxybutyrate
mitochondrial dysfunction
pathological proteins
neuro inflammation
