Neuropsychopharmacology Research Group, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, 2075 Bayview Avenue, Room FG52, Toronto, ON, M4N 3M5, Canada.
Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
Alzheimers Res Ther. 2022 Feb 5;14(1):23. doi: 10.1186/s13195-022-00961-5.
Increasing evidence implicates oxidative stress (OS) in Alzheimer disease (AD) and mild cognitive impairment (MCI). Depletion of the brain antioxidant glutathione (GSH) may be important in OS-mediated neurodegeneration, though studies of post-mortem brain GSH changes in AD have been inconclusive. Recent in vivo measurements of the brain and blood GSH may shed light on GSH changes earlier in the disease.
To quantitatively review in vivo GSH in AD and MCI compared to healthy controls (HC) using meta-analyses.
Studies with in vivo brain or blood GSH levels in MCI or AD with a HC group were identified using MEDLINE, PsychInfo, and Embase (1947-June 2020). Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated for outcomes using random effects models. Outcome measures included brain GSH (Meshcher-Garwood Point Resolved Spectroscopy (MEGA-PRESS) versus non-MEGA-PRESS) and blood GSH (intracellular versus extracellular) in AD and MCI. The Q statistic and Egger's test were used to assess heterogeneity and risk of publication bias, respectively.
For brain GSH, 4 AD (AD=135, HC=223) and 4 MCI (MCI=213, HC=211) studies were included. For blood GSH, 26 AD (AD=1203, HC=1135) and 7 MCI (MCI=434, HC=408) studies were included. Brain GSH overall did not differ in AD or MCI compared to HC; however, the subgroup of studies using MEGA-PRESS reported lower brain GSH in AD (SMD [95%CI] -1.45 [-1.83, -1.06], p<0.001) and MCI (-1.15 [-1.71, -0.59], z=4.0, p<0.001). AD had lower intracellular and extracellular blood GSH overall (-0.87 [-1. 30, -0.44], z=3.96, p<0.001). In a subgroup analysis, intracellular GSH was lower in MCI (-0.66 [-1.11, -0.21], p=0.025). Heterogeneity was observed throughout (I >85%) and not fully accounted by subgroup analysis. Egger's test indicated risk of publication bias.
Blood intracellular GSH decrease is seen in MCI, while both intra- and extracellular decreases were seen in AD. Brain GSH is decreased in AD and MCI in subgroup analysis. Potential bias and heterogeneity suggest the need for measurement standardization and additional studies to explore sources of heterogeneity.
越来越多的证据表明氧化应激（OS）与阿尔茨海默病（AD）和轻度认知障碍（MCI）有关。大脑抗氧化剂谷胱甘肽（GSH）的耗竭可能在 OS 介导的神经退行性变中很重要，尽管 AD 死后大脑 GSH 变化的研究尚无定论。最近对大脑和血液 GSH 的体内测量可能会更早地揭示疾病中的 GSH 变化。
使用荟萃分析定量比较 AD 和 MCI 与健康对照组（HC）的体内 GSH。
使用 MEDLINE、PsychInfo 和 Embase（1947 年-2020 年 6 月）检索 MCI 或 AD 中具有 HC 组的体内脑或血液 GSH 水平的研究。使用随机效应模型计算结局的标准化均数差（SMD）和 95%置信区间（CI）。结局指标包括 AD（AD=135，HC=223）和 MCI（MCI=213，HC=211）中脑 GSH（Meshcher-Garwood 点分辨波谱（MEGA-PRESS）与非 MEGA-PRESS）和血液 GSH（细胞内与细胞外）。Q 统计量和 Egger 检验分别用于评估异质性和发表偏倚的风险。
对于脑 GSH，纳入了 4 项 AD（AD=135，HC=223）和 4 项 MCI（MCI=213，HC=211）研究。对于血液 GSH，纳入了 26 项 AD（AD=1203，HC=1135）和 7 项 MCI（MCI=434，HC=408）研究。AD 和 MCI 的脑 GSH 总体上与 HC 无差异；然而，使用 MEGA-PRESS 的亚组研究报告 AD（SMD [95%CI]-1.45[-1.83，-1.06]，p<0.001）和 MCI（SMD [95%CI]-1.15[-1.71，-0.59]，z=4.0，p<0.001）脑 GSH 降低。AD 的血液细胞内和细胞外 GSH 总体降低（-0.87[-1.30，-0.44]，z=3.96，p<0.001）。在亚组分析中，MCI 的细胞内 GSH 降低（-0.66[-1.11，-0.21]，p=0.025）。整个研究都存在高度异质性（I>85%），且亚组分析无法完全解释异质性。Egger 检验表明存在发表偏倚的风险。
MCI 中可见血液细胞内 GSH 减少，而 AD 中可见细胞内和细胞外 GSH 减少。亚组分析中，AD 和 MCI 的脑 GSH 降低。潜在的偏倚和异质性表明需要进行标准化测量和进行更多的研究以探索异质性的来源。
