脑谷胱甘肽水平——轻度认知障碍和阿尔茨海默病的新型生物标志物。

Brain glutathione levels--a novel biomarker for mild cognitive impairment and Alzheimer's disease.

机构信息

Neuroimaging and Neurospectroscopy Laboratory, National Brain Research Centre, xxx, India; Department of Radiology and Radiological Science, Johns Hopkins Medicine, Baltimore, Maryland.

Neuroimaging and Neurospectroscopy Laboratory, National Brain Research Centre, xxx, India.

出版信息

Biol Psychiatry. 2015 Nov 15;78(10):702-10. doi: 10.1016/j.biopsych.2015.04.005. Epub 2015 Apr 14.

DOI:10.1016/j.biopsych.2015.04.005

PMID:26003861

Abstract

BACKGROUND

Extant data from in vivo animal models and postmortem studies indicate that Alzheimer's disease (AD) pathology is associated with reduction of the brain antioxidant glutathione (GSH), yet direct clinical evidence has been lacking. In this study, we investigated GSH modulation in the brain with AD and assessed the diagnostic potential of GSH estimation in hippocampi (HP) and frontal cortices (FC) as a biomarker for AD and its prodromal stage, mild cognitive impairment (MCI).

METHODS

Brain GSH levels were measured in HP of 21 AD, 22 MCI, and 21 healthy old controls (HC) and FC of 19 AD, 19 MCI, and 28 HC with in vivo proton magnetic resonance spectroscopy. The association between GSH levels and clinical measures of AD progression was tested. Linear regression models were used to determine the best combination of GSH estimation in these brain regions for discrimination between AD, MCI, and HC.

RESULTS

AD-dependent reduction of GSH was observed in both HP and FC (p < .001). Furthermore, GSH reduction in these regions correlated with decline in cognitive functions. Receiver operator characteristics analyses evidenced that hippocampal GSH robustly discriminates between MCI and healthy controls with 87.5% sensitivity, 100% specificity, and positive and negative likelihood ratios of 8.76/.13, whereas cortical GSH differentiates MCI and AD with 91.7% sensitivity, 100% specificity, and positive and negative likelihood ratios of 9.17/.08.

CONCLUSIONS

The present study provides compelling in vivo evidence that estimation of GSH levels in specific brain regions with magnetic resonance spectroscopy constitutes a clinically relevant biomarker for MCI and AD.

摘要

背景

来自体内动物模型和尸检研究的现有数据表明，阿尔茨海默病（AD）病理学与大脑抗氧化剂谷胱甘肽（GSH）的减少有关，但缺乏直接的临床证据。在这项研究中，我们研究了 AD 患者大脑中的 GSH 调节，并评估了 GSH 估计在海马（HP）和额皮质（FC）中的诊断潜力，作为 AD 及其前驱阶段轻度认知障碍（MCI）的生物标志物。

方法

使用体内质子磁共振波谱法测量了 21 例 AD、22 例 MCI 和 21 例健康老年对照组（HC）的 HP 中的脑 GSH 水平，以及 19 例 AD、19 例 MCI 和 28 例 HC 的 FC 中的脑 GSH 水平。测试了 GSH 水平与 AD 进展临床测量之间的相关性。线性回归模型用于确定这些脑区中 GSH 估计的最佳组合，以区分 AD、MCI 和 HC。

结果

在 HP 和 FC 中均观察到 AD 依赖性 GSH 减少（p<0.001）。此外，这些区域的 GSH 减少与认知功能下降相关。受试者工作特征分析表明，海马 GSH 对 MCI 和健康对照组具有强大的区分能力，敏感性为 87.5%，特异性为 100%，阳性和阴性似然比分别为 8.76/0.13，而皮质 GSH 对 MCI 和 AD 的区分能力为 91.7%，特异性为 100%，阳性和阴性似然比分别为 9.17/0.08。