Ebrahimi Rasoul, Mohammad Soltani Sana, Masouri Mohammad Mahdi, Seifi Mojtaba, Ghafourian Kiana, Noori Shokoofe
Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
BMC Neurol. 2025 Aug 26;25(1):344. doi: 10.1186/s12883-025-04375-2.
This systematic review and meta-analysis compares glutamate, glutamine, and GABA levels in cerebrospinal fluid (CSF), blood, and brain tissue between individuals with Alzheimer's disease (AD) and cognitively unimpaired (CU) controls.
We systematically searched PubMed and Web of Science up to February 20, 2025, for studies reporting GABA, glutamate, or glutamine levels in AD and CU controls. Effect sizes were calculated using Hedges' g, with heterogeneity assessed via I² statistics and publication bias evaluated using funnel plots and Egger's and Begg's tests.
From 14,857 records, 53 studies were included. Glutamate levels were significantly lower in AD brains, including the cortex (SMD = - 0.42; 95% CI [-0.79, - 0.05]; I² = 67.26%; p = 0.03), hippocampus (SMD = - 0.56; 95% CI [-0.91, - 0.20]; I² = 37.29%; p < 0.05), and temporal cortex (SMD = - 0.87; 95% CI [-1.52, - 0.23]; I² = 77.60%; p = 0.01), but not in CSF or blood. Glutamine showed no significant differences in brain regions, CSF, or blood. GABA levels were significantly lower in AD patients across the cortex (SMD = - 0.53; 95% CI [-0.81, - 0.25]; I² = 58.60%; p < 0.05), CSF (SMD = - 0.38; 95% CI [-0.65, - 0.11]; I² = 0.00%; p = 0.01), and blood (SMD = - 0.72; 95% CI [-1.08, - 0.37]; I² = 43.18%; p < 0.05).
Our findings underscore the potential of targeting glutamatergic and GABAergic systems in AD clinical research. We recommend prioritizing future investigations in earlier disease stages, such as preclinical AD and mild cognitive impairment.
本系统评价和荟萃分析比较了阿尔茨海默病（AD）患者与认知未受损（CU）对照者脑脊液（CSF）、血液和脑组织中谷氨酸、谷氨酰胺和γ-氨基丁酸（GABA）的水平。
我们系统检索了截至2025年2月20日的PubMed和Web of Science，以查找报告AD患者和CU对照者中GABA、谷氨酸或谷氨酰胺水平的研究。使用Hedges' g计算效应量，通过I²统计量评估异质性，并使用漏斗图以及Egger检验和Begg检验评估发表偏倚。
从14,857条记录中，纳入了53项研究。AD患者大脑中的谷氨酸水平显著较低，包括皮质（标准化均数差[SMD]= -0.42；95%置信区间[-0.79, -0.05]；I² = 67.26%；p = 0.03）、海马体（SMD = -0.56；95%置信区间[-0.91, -0.20]；I² = 37.29%；p < 0.05）和颞叶皮质（SMD = -0.87；95%置信区间[-1.52, -0.23]；I² = 77.60%；p = 0.01），但在CSF或血液中未发现显著差异。谷氨酰胺在脑区、CSF或血液中均未显示出显著差异。AD患者整个皮质（SMD = -0.53；95%置信区间[-0.81, -0.25]；I² = 58.60%；p < 0.05）、CSF（SMD = -0.38；95%置信区间[-0.65, -0.11]；I² = 0.00%；p = 0.01）和血液（SMD = -0.72；95%置信区间[-1.08, -0.37]；I² = 43.18%；p < 0.05）中的GABA水平均显著较低。
我们的研究结果强调了在AD临床研究中靶向谷氨酸能和GABA能系统的潜力。我们建议优先在疾病早期阶段进行未来的研究，如临床前AD和轻度认知障碍。
