Detcheverry Flavie E, Senthil Sneha, Motue Winnie L K, Hosein Chris, Arnaoutelis Rozie, Araujo David, Fetco Dumitru, Assemlal Haz-Edine, Antel Samson, Arnold Douglas L, Near Jamie, Schipper Hyman M, Badhwar AmanPreet, Narayanan Sridar
Multiomics Investigation of Neurodegenerative Diseases (MIND) lab, Montreal, Quebec, Canada.
Department of Pharmacology and Physiology, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada.
Alzheimers Dement. 2025 Sep;21(9):e70456. doi: 10.1002/alz.70456.
Oxidative stress may contribute to brain injury in the Alzheimer's disease (AD) continuum. The antioxidant glutathione (GSH) can be assessed with magnetic resonance spectroscopy (MRS). Because the relationship between GSH and vascular brain injury is unknown in the AD continuum, we address this gap in mild cognitive impairment (MCI).
3T Magnetic resonance imaging (MRI)/MRS data were obtained from 31 patients with MCI. GSH and total N-acetylaspartate (tNAA; neuroaxonal integrity marker) were measured in posterior cingulate cortex (PCC) and frontal white matter (FWM). Cerebrovascular injury was assessed using white matter hyperintensity (WMH) volume. Global and regional brain tissue integrity were assessed using normalized brain (NBV) and hippocampal volumes.
Significant associations were reported in FWM between GSH/total creatine (tCr) and tNAA/tCr, and between GSH and both WMH and NBV. tNAA, GSH/tCr, and tNAA/tCr were higher in PCC than in FWM.
Our results suggest that oxidative stress contributes to vascular brain injury in MCI.
Neuronal, vascular, and oxidative injuries occur in the Alzheimer's disease (AD) spectrum. Glutathione (GSH) is the main endogenous antioxidant in the brain. Brain GSH can be measured with magnetic resonance spectroscopy (MRS). We measured brain GSH level in people with mild cognitive impairment (MCI). Low GSH level was associated with vascular brain injury, neuroaxonal damage, and atrophy.
氧化应激可能在阿尔茨海默病（AD）连续体中导致脑损伤。抗氧化剂谷胱甘肽（GSH）可通过磁共振波谱（MRS）进行评估。由于在AD连续体中GSH与脑微血管损伤之间的关系尚不清楚，我们在轻度认知障碍（MCI）中解决了这一空白。
从31例MCI患者中获取3T磁共振成像（MRI）/MRS数据。在扣带回后部（PCC）和额叶白质（FWM）中测量GSH和总N-乙酰天门冬氨酸（tNAA；神经轴突完整性标志物）。使用白质高信号（WMH）体积评估脑血管损伤。使用标准化脑体积（NBV）和海马体积评估全脑和局部脑组织完整性。
在FWM中，GSH/总肌酸（tCr）与tNAA/tCr之间以及GSH与WMH和NBV之间均存在显著相关性。PCC中的tNAA、GSH/tCr和tNAA/tCr高于FWM。
我们的结果表明氧化应激在MCI中导致脑微血管损伤。
在阿尔茨海默病（AD）谱系中发生神经元、血管和氧化损伤。谷胱甘肽（GSH）是脑中主要的内源性抗氧化剂。脑GSH可用磁共振波谱（MRS）测量。我们测量了轻度认知障碍（MCI）患者的脑GSH水平。低GSH水平与脑微血管损伤、神经轴突损伤和萎缩相关。
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