Journal of Modern Biotechnology Research
Journal of Modern Biotechnology Research. 2025; 3: (1) ; 10.12208/j.jmbr.20250003 .
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1延安大学 陕西延安
2陕西省区域生物资源保育与利用工程技术研究中心 陕西延安
*通讯作者： 白占涛,单位：延安大学 陕西延安 陕西省区域生物资源保育与利用工程技术研究中心 陕西延安；
阿尔兹海默病（Alzheimer's disease, AD）作为全球范围内最多见的神经退行性疾病，表现为进行性认知功能衰退。新近研究表明代谢稳态失衡与AD病理进程密切关联，且脑内乳酸异常蓄积与认知功能障碍程度呈显著正相关性。星形胶质细胞作为中枢神经系统内主要的乳酸生成细胞，通过星形胶质细胞-神经元乳酸穿梭（ANLS）机制维持神经元能量稳态。AD病理状态下，ANLS系统功能紊乱导致乳酸生成/清除动态平衡破坏，形成病理性乳酸蓄积，通过激活β-分泌酶、促进Aβ沉积、加剧Tau蛋白异常磷酸化、触发神经炎症及氧化应激等多重途径，加速神经元损伤和突触功能障碍而加重AD病程。乳酸水平积蓄性上升成为 AD 早期诊断新的重要病理标志物。基于此，本文综述了乳酸与乳酸穿梭和AD病理的关联机理，以深刻理解AD发生代谢机并提出新型AD诊疗策略。
Alzheimer's disease (AD), the most common neurodegenerative disease in the world, is characterized by progressive cognitive decline. Recent studies have shown that the imbalance of metabolic homeostasis is closely related to the pathological process of AD, and the abnormal accumulation of lactic acid in the brain is significantly positively correlated with the degree of cognitive dysfunction. Astrocytes, as the main lactate producing cells in the central nervous system, maintain neuronal energy homeostasis through the astro-neuronal lactate shuttle (ANLS) mechanism. In the pathological state of AD, the dysfunction of the ANLS system leads to the breakdown of the dynamic balance of lactic acid production/clearance and the formation of pathological lactic acid accumulation, which accelerates neuronal damage and synaptic dysfunction through multiple pathways such as activating β-secretase, promoting Aβ deposition, intensifying abnormal phosphorylation of Tau protein, triggering neuroinflammation and oxidative stress. The accumulated increase of lactic acid level has become a new important pathological marker for the early diagnosis of AD. Based on this, this paper reviews the correlation mechanism between lactic acid and lactic acid shuttle and AD pathology, so as to deeply understand the pathogenesis of AD and propose new diagnosis and treatment strategies for AD.
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