Rasoul Ebrahimi, Sana Mohammad Soltani, Mohammad Mahdi Masouri, Mojtaba Seifi, Kiana Ghafourian, Shokoofe Noori
{"title":"阿尔茨海默病的谷氨酸能和gaba能代谢物水平:系统回顾和荟萃分析","authors":"Rasoul Ebrahimi, Sana Mohammad Soltani, Mohammad Mahdi Masouri, Mojtaba Seifi, Kiana Ghafourian, Shokoofe Noori","doi":"10.1186/s12883-025-04375-2","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and objectives: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":9170,"journal":{"name":"BMC Neurology","volume":"25 1","pages":"344"},"PeriodicalIF":2.2000,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12379390/pdf/","citationCount":"0","resultStr":"{\"title\":\"Glutamatergic and GABAergic metabolite levels in Alzheimer's disease: a systematic review and meta-analysis.\",\"authors\":\"Rasoul Ebrahimi, Sana Mohammad Soltani, Mohammad Mahdi Masouri, Mojtaba Seifi, Kiana Ghafourian, Shokoofe Noori\",\"doi\":\"10.1186/s12883-025-04375-2\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background and objectives: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>Our findings underscore the potential of targeting glutamatergic and GABAergic systems in AD clinical research. 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引用次数: 0
摘要
背景和目的:本系统综述和荟萃分析比较了阿尔茨海默病(AD)患者和认知功能未受损(CU)对照者脑脊液(CSF)、血液和脑组织中谷氨酸、谷氨酰胺和GABA的水平。方法:我们系统地检索PubMed和Web of Science,直到2025年2月20日,以报道AD和CU对照中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统计评估异质性,使用漏斗图和Egger's和Begg's检验评估发表偏倚。结果:从14857份记录中,纳入53项研究。AD大脑中谷氨酸水平显著降低,包括皮层(SMD = - 0.42; 95% CI [-0.79, - 0.05]; I²= 67.26%;p = 0.03)和海马(SMD = - 0.56; 95% CI [-0.91, - 0.20]; I²= 37.29%;p结论:我们的研究结果强调了在AD临床研究中针对谷氨酸能和gaba能系统的潜力。我们建议优先考虑早期疾病阶段的研究,如临床前AD和轻度认知障碍。
Glutamatergic and GABAergic metabolite levels in Alzheimer's disease: a systematic review and meta-analysis.
Background and objectives: 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.
Methods: 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.
Results: 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).
Conclusion: 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.
期刊介绍:
BMC Neurology is an open access, peer-reviewed journal that considers articles on all aspects of the prevention, diagnosis and management of neurological disorders, as well as related molecular genetics, pathophysiology, and epidemiology.