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阿尔茨海默病中的GABAergic系统:通过元分析进行系统性审查

Giovanna Carello-Collar¹, Bruna Bellaver^1,2, Pamela C L Ferreira²

¹Graduate Program in Biological Sciences: Biochemistry, Department of Biochemistry, Institute of Health Basic Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, 90035-003, Brazil.

Molecular psychiatry

|July 7, 2023

概括

阿尔茨海默病 (AD) 患者在大脑和脑脊液 (CSF) 中显示抑制性神经递质胺黄油酸 (GABA) 的水平降低. 这表明GABAergic系统是新的AD治疗和生物标志物的潜在目标.

科学领域:

神经科学是一个神经科学.
生物化学生物化学
病理学病理学病理学

背景情况:

胺黄油酸 (GABA) 能系统对于哺乳动物大脑中抑制性神经传递至关重要.
GABAergic系统的失调与各种神经疾病有关,在阿尔茨海默病 (AD) 中有相互矛盾的证据.

研究的目的:

与健康对照组 (HC) 相比,系统地审查和元分析研究,调查阿尔茨海默病患者GABAergic系统的变化.
评估GABAergic系统作为AD治疗标和生物标记物的潜力.

主要方法:

在PubMed和Web of Science的系统文献搜索 (截至2023年3月18日) 寻找关于AD的GABA,GAD65/67,GABA受体和GABA载体的研究.
包括48项研究,518名HC和603名AD患者.
随机效应元分析使用标准化平均差异 (SMD) 来比较组之间的GABAergic成分.

主要成果:

艾滋病患者在大脑 (SMD = -0.48) 和脑液 (SMD = -0.41) 中的GABA水平显著降低.
在AD患者和HC患者之间没有发现血液GABA水平的显著差异.
在AD大脑中观察到降低了谷氨酸脱酶65/67 (GAD65/67) (SMD = -0.67),GABA_A受体 (SMD = -0.51) 和GABA载体 (SMD = -0.51) 的水平.

结论:

该GABAergic系统显示大脑内成分的总体减少和AD患者的CSF的GABA水平下降.
这些发现凸显了GABAergic系统对AD病理学的脆弱性.
对于阿尔茨海默病的新药学策略和生物标志物来说,GABAergic系统是一个有前途的目标.

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