A study has identified two forms of glutathione (GSH) — an important antioxidant that protects the brain from harmful free radicals — in the brains of living people using a non-invasive technique. It also found one form of GSH at levels significantly lower than usual in people with Alzheimer’s disease (AD). Its non-invasive technique was based on magnetic resonance spectroscopy — an ionizing-radiation-free technique that allows the study of metabolic changes in the brain — and may serve as an important diagnostic tool. The study, “A Multi-Center Study on Human Brain Glutathione Conformation using Magnetic Resonance Spectroscopy,” was published in the Journal of Alzheimer’s Disease. High levels of cellular oxidative stress — a disproportion between free radicals (potentially harmful, unstable molecules) and antioxidants (molecules that can stabilize free radicals) — are increasingly associated with age-related diseases, namely neurodegenerative disorders such as AD. In fact, strong evidence, mostly coming from postmortem studies, sow that AD patients’ brains are depleted of GSH compared to controls. A team led by researchers at the National Brain Research Center in India, and Case Western Reserve University in Ohio conducted an in-depth analysis of GSH in 29 healthy adults. Data was collected using magnetic resonance spectroscopy (MRS), a non-invasive technique that measures molecular substances (metabolites) in living tissues, including the brain. Each metabolite translates to a peak. GSH levels are difficult to detect as this metabolite exists in low concentrations in the brain. As such, researchers took a new approach and combined optimal MRS parameters (based on previous studies) with MEGA-PRESS pulse sequence — a spectroscopy technique previously shown to be useful in identifying GSH in the brain. Results confirmed what researchers had previously observed in lab experiments, the existence of two conformational peaks for GSH in the brain. One peak corresponded to a closed and more stable conformation of GSH, and the other one to an extended form of the metabolite. "This is the first report providing important evidence for the co-existence of two in vivo GSH conformations in the human brain," the researchers wrote. When GSH is depleted in the hippocampus (a brain region involved in memory and learning) of an elderly person, the brain suffers mild cognitive impairment. Such mild cognitive impairment is known to be present in earlier Alzheimer's stages. Researchers also found that the closed conformation of GSH is depleted in AD patients. They suggest that using their technique to assess GSH levels in Alzheimer's patients could help in disease management. "If routine non-invasive tests for lower levels of GSH in the hippocampus regions are performed, we might be able to mitigate the advancement of Alzheimer's disease by providing GSH supplements,” Pravat Mandal, PhD, the study's lead author, said in a press release. "Our work is expected to have a huge impact on the understanding of GSH and its profound role in the individual’s cognitive reserve," the researchers wrote. Cognitive reserve is a person's capacity to maintain normal cognitive function. "Furthermore observational studies on GSH supplement and its impact on cognitive reserve for healthy old and mild cognitive impairment patients" is planned, the team added.