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Brain Glutathione Levels – A Novel Biomarker for Mild Cognitive Impairment and Alzheimer’s Disease

  • Pravat K. Mandal
    Correspondence
    Address correspondence to: Dr. Pravat K Mandal, Neuroimaging and Neurospectroscopy Laboratory, National Brain Research Centre, India and Adjunct Associate Professor, Department of Radiology and Radiological Science, Johns Hopkins Medicine, Baltimore, MD, USA.
    Affiliations
    Neuroimaging and Neurospectroscopy Laboratory, National Brain Research Centre, xxx, India

    Department of Radiology and Radiological Science, Johns Hopkins Medicine, Baltimore, Maryland
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  • Sumiti Saharan
    Affiliations
    Neuroimaging and Neurospectroscopy Laboratory, National Brain Research Centre, xxx, India
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  • Manjari Tripathi
    Affiliations
    Department of Neurology, All India Institute of Medical Sciences, New Delhi, India
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  • Geetanjali Murari
    Affiliations
    Neuroimaging and Neurospectroscopy Laboratory, National Brain Research Centre, xxx, India
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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.

      Keywords

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      • Erratum
        Biological PsychiatryVol. 79Issue 1
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          An error in the text been detected in the article “Brain Glutathione Levels – A Novel Biomarker for Mild Cognitive Impairment and Alzheimer’s Disease” by Mandal et al. (2015; 78:702-710). Specifically, there is a typographical error in the Acknowledgments & Disclosures section (page 708, column 2). The final sentence of the first paragraph in this section should read: “Dr. Mandal dedicated this work in honor of his parents (Mr. Bhadreswar Mandal and Mrs. Kalpana Mandal).”
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