The idea that antioxidants play a large role in the development and progression of Alzheimer’s disease (AD) is not new. However, researchers have met with difficulties in efficiently monitoring the free-radical scavenging molecules in the brain. Yet now, new evidence from investigators at the National Brain Research Centre in Gurgaon, India, shows that the antioxidant, glutathione (GSH), which protects the brain from stress, has been found to be significantly depleted in Alzheimer's patients compared to normal subjects. Moreover, the scientists have used a noninvasive technique called magnetic resonance spectroscopy (MRS) to accurately track GSH levels in the brain.        

Findings from the new study were published recently in the Journal of Alzheimer’s Disease through an article titled “A Multi-Center Study on Human Brain Glutathione Conformation using Magnetic Resonance Spectroscopy.”

“The present work in a multicenter research setting reports an in-depth analysis of GSH conformers in vivo using a common MRS protocol and signal processing scheme. MEGA-PRESS pulse sequence was applied on healthy subjects using 3T Philips MRI scanner (India) and 3T GE MRI scanner (Norway) using the same experimental parameters (echo time, repetition time, and selective 180° refocusing ON-pulse at 4.40 ppm and 4.56 ppm),” the authors wrote. “All MRS data were processed at one site National Brain Research Center (NBRC) using in-house MRS processing toolbox (KALPANA) for consistency.”

By implementing these noninvasive imaging techniques, the researchers found that GSH has two conformations (closed and extended forms) in the brain. It was discovered that when GSH is depleted in the hippocampus regions of an elderly person the healthy brain suffers mild cognitive impairment (MCI), which is known to be present in the earlier stages of AD. It is now correlated that closed form of GSH is depleted in AD patients. At present no report is available to indicate to what extent the lower levels of the extended form of GSH in those suffering from AD can be measured but it opens the possibility for further clinical observation using GSH as a supplement to combat the advancement of AD.

“We have found that both the closed and extended GSH conformations are present in human brain and the relative proportion of individual conformer peak depends on the specific selection of refocusing ON-pulse position in MEGA-PRESS pulse sequence,” the authors penned. “It is important to emphasize that in vivo experiments with different refocusing and inversion pulse positions, echo time, and voxel size, show clear evidence in the presence of both the GSH conformations.”

The authors continued, stating that “this is the first in vivo study where both extended and closed GSH conformers are detected using the MEGA-PRESS sequence employing the parameters derived from the high-resolution in vitro NMR studies on GSH.”

The investigators were encouraged by their findings and believe that their research could have huge potential in therapeutic developments for Alzheimer’s disease.

“If routine noninvasive 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—an observational study is planned,” concluded co-lead study investigator Pravat Mandal, Ph.D., a fellow at the Florey Institute of Neuroscience and Mental Health in Melbourne.

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