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Mandal, PK and Saharan, S and Tripathi, M and Murari, G (2015) Brain glutathione levels--a novel biomarker for mild cognitive impairment and Alzheimer's disease. Biol Psychiatry, 78. pp. 702-710.

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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.

Item Type: Article
Subjects: Neurodegenerative Disorders
Neuro-Oncological Disorders
Neurocognitive Processes
Neuronal Development and Regeneration
Informatics and Imaging
Genetics and Molecular Biology
Depositing User: Dr. D.D. Lal
Date Deposited: 12 Jul 2017 06:44
Last Modified: 17 Sep 2018 05:20
URI: http://nbrc.sciencecentral.in/id/eprint/203

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