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, including β-amyloid deposition, hyperphosphorylated tau aggregation, 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 pathological targets central to AD progression. This review systematically summarizes the neuroprotective mechanisms of BHB in AD, focusing on mitochondrial dysfunction, pathological protein deposition, neuroinflammation, oxidative stress, and insulin resistance. Clinical studies indicate that BHB significantly improves cognition in APOE ε4-negative patients, yet current strategies for inducing endogenous ketosis or supplementing exogenous ketones face substantial challenges. Future research should focus on optimizing BHB administration 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.