Dr. Joseph Maroon Co-Authors Alzheimers Disease Article on Oxidative stress Hypothesis of AD

January 22, 2025 Neurosurgeon and Neuroscience Researcher, Dr. Joseph Maroon, along with lead author, Pravat K Mandal, PhD, at the University of Pittsburgh Medical Center, have just published a profound article on Alzheimer’s disease (AD) in the journal ASC Chemical Neuroscience.  The article, entitled, The Missing Link in Antiamyloid Therapy, puts forth the concept that oxidative stress, a type of inflammation, associate with Alzheimer’s disease, is a critical and destructive factor for the cognitive decline associated with this disease.

The oxidative stress  hypothesis, is in part due to autopsy data that reports significant depletion of the master antioxidant glutathione (GSH) in the hippocampal region of the brain. And is believed to be an early event in AD progression.

In the abstract of the article they note: “Hippocampal GSH depletion is positively correlated with memory impairment. We have confirmed non-invasively with magnetic resonance spectroscopy (MRS) the depletion of GSH in patients with MCI and AD. We therefore propose a combinational therapy involving oral supplementation of gamma-glutamylcysteine (GGC), an early precursor of glutathione, to replenish brain GSH in addition to lecanemab, potentially to maximize desirable outcomes from combined therapeutic approach.”

The concept of using and studying the use of the antioxidant Glutathione, using a oral supplement, has been tried with various results.    Uniquely, in this article, Maroon, et al, propose a human study involving healthy adults with oral supplementation of antioxidant gamma-glutamylcysteine (GGC), a precursor to GSH.

A preclinical study tested the impact of GGC on  a type of mouse that have been genetically modified to have human genes associated with early-onset Alzheimer’s disease.  They found that these mice treated with GGC demonstrated significant improvement of spatial memory performance compared to placebo. It is hoped that funding for a human study will soon be started based on these encouraging results.

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