title: Brain glutathione levels--a novel biomarker for mild cognitive impairment and Alzheimer's disease.
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.
authors.affiliation: Neuroimaging and Neurospectroscopy Laboratory, National Brain Research Centre, xxx, India; Department of Radiology and Radiological Science, Johns Hopkins Medicine, Baltimore, Maryland. Electronic address: pmandal4@jhmi.edu.
authors.forename: Pravat K
authors.initials: PK
authors.lastname: Mandal
authors.affiliation: Neuroimaging and Neurospectroscopy Laboratory, National Brain Research Centre, xxx, India.
authors.forename: Sumiti
authors.initials: S
authors.lastname: Saharan
authors.affiliation: Department of Neurology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Manjari
authors.initials: M
authors.lastname: Tripathi
authors.affiliation: Neuroimaging and Neurospectroscopy Laboratory, National Brain Research Centre, xxx, India.
authors.forename: Geetanjali
authors.initials: G
authors.lastname: Murari
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000378:metabolism; D015415:Biomarkers; D001921:Brain / Q000378:metabolism*; D060825:Cognitive Dysfunction / Q000175:diagnosis* / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D016013:Likelihood Functions; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D066244:Proton Magnetic Resonance Spectroscopy; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D005978:Glutathione
keywords: Alzheimer’s disease; Biomarker; GSH; MEGA-PRESS; Mild cognitive impairment; Noninvasive