Longitudinal Monitoring of Glutathione Stability in Different Microenvironments

Glutathione (GSH) is a master antioxidant which primarily protects cells from oxidative stress. Clinical studies have found significant depletion of GSH from the hippocampus in patients with mild cognitive impairment (MCI), a transitional stage before conversion to Alzheimer's disease (AD). Significant depletion of GSH is considered an early diagnostic biomarker of AD. Postmortem studies have confirmed significant GSH depletion in hippocampal tissue in MCI patients. The stability of GSH in different microenvironments is essential to validate GSH as a reliable biomarker for AD. Accordingly, we have conducted longitudinal monitoring of GSH from various brain regions (frontal cortex (FC), parietal cortex (PC), occipital cortex (OC), and cerebellum (CER)) from healthy subjects using MEshcher-GArwood Point RESolved Spectroscopy (MEGA-PRESS) pulse sequence on a 3T scanner. Additionally, in vitro magnetic resonance spectroscopy (MRS) assessments were conducted longitudinally using the same study protocol involving GSH supplement in a physiologically relevant phosphate buffer solution (PBS). We report that GSH within the brain microenvironment of a healthy person remains stable over time. GSH, however, is susceptible to oxidation over time in a phosphate buffer environment. The stability of GSH in a longitudinal study in the brains of healthy individuals supports the consideration of GSH as a candidate for stable biomarker for AD.