Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Department of Surgery, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA.
J Neurosci Res. 2024 Sep;102(9):e25380. doi: 10.1002/jnr.25380.
The findings concerning the association between endocannabinoid system (ECS) and Alzheimer's disease (AD) exhibited inconsistencies when examining the expression levels of endocannabinoids. This study aimed to provide a comprehensive summary of the studies regarding alterations of the ECS in AD. Six databases were thoroughly searched for literature to select relevant studies investigating the ECS in AD, including changes in cannabinoid receptors (CB1R and CB2R), endocannabinoids (2-AG and AEA), and their associated enzymes (FAAH and MAGL). Traditional meta-analysis evaluated the expression levels of the ECS in AD, and the results showed no significant differences in ECS components between healthy controls and AD patients. However, subgroup analysis revealed significantly lower expression levels of CB1R in AD than in controls, particularly in studies using western blot (SMD = -0.88, p < 0.01) and in studies testing CB1R of frontal cortex (SMD = -1.09, p < 0.01). For studies using HPLC, the subgroup analysis indicated significantly higher 2-AG levels in AD than in controls (SMD = 0.46, p = 0.02). Network meta-analysis examined the rank of ECS alterations in AD compared to controls, and the findings revealed that 2-AG and MAGL exhibited the largest increase and CB1R showed the largest decrease relative to the control group. Based on the findings of traditional meta-analysis and network meta-analysis, we proposed that AD patients may present decreased expression levels of CB1R and increased expression levels of 2-AG and its degrading enzyme MAGL. Our results may contribute to the growing body of research supporting the therapeutic potential of ECS modulation in the management of AD.
关于内源性大麻素系统 (ECS) 与阿尔茨海默病 (AD) 之间的关联，在检测内源性大麻素的表达水平时，研究结果并不一致。本研究旨在对 AD 中 ECS 改变的相关研究进行全面总结。为了选择研究 AD 中 ECS 的相关文献，我们彻底搜索了六个数据库，包括大麻素受体 (CB1R 和 CB2R)、内源性大麻素 (2-AG 和 AEA) 及其相关酶 (FAAH 和 MAGL) 的变化。传统的荟萃分析评估了 AD 中 ECS 的表达水平，结果显示健康对照组和 AD 患者之间 ECS 成分无显著差异。然而，亚组分析显示 AD 患者的 CB1R 表达水平显著低于对照组，尤其是在使用western blot 的研究中 (SMD=-0.88, p<0.01) 和在检测额皮质 CB1R 的研究中 (SMD=-1.09, p<0.01)。对于使用 HPLC 的研究，亚组分析表明 AD 患者的 2-AG 水平显著高于对照组 (SMD=0.46, p=0.02)。网络荟萃分析比较了 AD 与对照组相比 ECS 改变的等级，结果表明 2-AG 和 MAGL 的增加幅度最大，而 CB1R 相对于对照组的下降幅度最大。基于传统荟萃分析和网络荟萃分析的结果，我们提出 AD 患者可能表现出 CB1R 表达水平降低和 2-AG 及其降解酶 MAGL 表达水平升高。我们的研究结果可能有助于支持 ECS 调节在 AD 治疗中的潜在治疗作用的研究不断增加。
