Alzheimer’s Disease: A Review of Pathology, Current Treatments, and the Potential Therapeutic Effect of Decreasing Oxidative Stress by Combined Vitamin D and L-Cysteine Supplementation

Excess oxidative stress and neuro-inflammation are risk factors in the onset and progression of AD and its association with amyloid- (A) plaque accumulation. Oxidative stress impairs acetylcholine (ACH) and N-methyl-D-aspartate receptor (NMDA receptor) signaling in brain areas that function in memory and learning. Glutathione (GSH) antioxidant depletion positively correlates with the cognitive decline in AD subjects. Treatments that upregulate GSH and ACH levels, which simultaneously decrease oxidative stress and inflammation, may be beneficial for AD.Some clinical trials have shown a benefit of monotherapy with Vitamin D (VD), whose deficiency is linked to AD or with L-cysteine (LC), a precursor of GSH biosynthesis, in reducing mild cognitive impairment (MCI). Animal studies have shown a simultaneous decrease in ACH esterase (ACHE) and increase in GSH; combined supplementation with VD and LC results in a greater decrease in oxidative stress and inflammation and increase in GSH levels compared to monotherapy with VD or LC. Therefore, co-supplementation with VD and LC has the potential of increasing GSH, downregulation of oxidative stress and decreased inflammation levels.Clinical trials are needed to determine whether safe-low-cost dietary supplements, using combined VD+LC, have the potential to alleviate elevated oxidative stress, and inflammation levels and thereby halt the onset of AD. Goal of Review. The goal of this review is to highlight the pathological hallmarks and current FDA approved treatments for AD and discuss the potential therapeutic effect that co-supplementation with VD+LC could manifest by increasing GSH levels in patients.