Reducing iron, adding antioxidants may help prevent Alzheimer's disease

Friday, April 13, 2012. A report published online on March 9, 2012 in the Journal of Alzheimer's Disease describes research conducted by Othman Ghribi, PHD of the University of North Dakota and his associates which suggests that lowering iron levels and supplementing with antioxidants could help protect the brain from some of the changes related to the development of Alzheimer's disease.

"The causes of Alzheimer's disease are not well known but a number of environmental and dietary factors are suggested to increase the risk of developing Alzheimer's disease," the authors write in their introduction to the article. "Additionally, altered metabolism of iron may have a role in the pathogenesis of Alzheimer's disease."

In previous research, Dr Ghribi's team demonstrated that the intake of a high cholesterol diet results in Alzheimer's disease-like changes and iron deposition in the brains of experimental animals. In the current study, rabbits were given a high cholesterol diet for 12 weeks, which resulted in the formation of brain plaques containing the protein amyloid beta, which is a characteristic of Alzheimer's disease. The animals also underwent increased phosphorylation of a protein in the brain's neurons known as tau, which is another hallmark of the disease. When some of the rabbits were treated with the iron-chelating agent deferiprone, plasma cholesterol and iron levels were lowered, and even though brain iron levels were not also reduced, amyloid beta and phosphorylated tau were significantly decreased. Treatment with deferiprone did not reduce levels of reactive oxygen species (whose generation by iron causes damage to neurons) in comparison with untreated animals. "These results demonstrate that deferiprone confers important protection against hypercholesterolemia-induced Alzheimer's disease pathology but the mechanism(s) may involve reduction in plasma iron and cholesterol levels rather than chelation of brain iron," the authors conclude. "We propose that adding an antioxidant therapy to deferiprone may be necessary to fully protect against cholesterol-enriched diet-induced Alzheimer's disease-like pathology."

"Our data show that treatment with the iron chelator deferiprone opposes several pathological events induced by a cholesterol-enriched diet," commented Dr Ghribi, who is an associate professor at the University of North Dakota School of Medicine and Health Sciences' department of pharmacology, physiology, and therapeutics. "Deferiprone reduced the generation of amyloid beta and lowered levels of tau phosphorylation."

"It is possible that a higher dose of deferiprone, or combination therapy of deferiprone together with an antioxidant to prevent reactive oxygen species generation would more fully protect against the deleterious effects of cholesterol-enriched diet that are relevant to Alzheimer's disease pathology," he added.