Iron build-up in the brain linked to age-related cognitive decline

February 3, 2022

The accumulation or iron in the brains of aging organisms is said to contribute to neurodegenerative diseases including Alzheimer’s disease. According to researchers at Northwestern University Feinberg School of Medicine (Northwestern), treatment with drugs called iron chelators could combat neurodegenerative diseases and restore normal iron metabolism in those experiencing high iron levels.

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Iron build-up in the brain linked to age-related cognitive decline

The accumulation or iron in the brains of aging organisms is said to contribute to neurodegenerative diseases including Alzheimer’s disease. According to researchers at Northwestern University Feinberg School of Medicine (Northwestern), treatment with drugs called iron chelators could combat neurodegenerative diseases and restore normal iron metabolism in those experiencing high iron levels.

In a study of young and old mice, Northwestern researchers found the brain was the only organ which showed an increase in cellular iron concentrations as the animals aged.

“There is tight regulation of iron homeostasis (metabolism) in the brain, but it appears that this regulation is disrupted as we age,” said Professor Dr. Hossein Ardehali, Division of Cardiology and Pharmacology, Northwestern.

A colleague of Dr. Ardehali’s later discovered the upregulation of iron in key brain areas relating to cognition was due to increased production of the protein hepcidin in the brain. Hepcidin, in turn, was found to inhibit the activity of a protein called ferroportin, which helps regulate neuronal iron levels.

In short, the increased production of hepcidin and decreased activity in ferroportin results in heightened iron concentrations within the brain. It has also been established that heightened iron concentrations within the brain can induce oxidative damage and enhance cell death.

A possible therapeutic strategy is the use of iron chelators – substances that bind to iron and make it biologically unavailable — to treat iron accumulation in the brain, said Dr. Ardehali. Iron chelators are as yet unable to cross the blood-brain barrier, however, there is an ongoing clinical trial assessing the effects of a specific iron chelator that can cross the barrier, in Parkinson’s disease.

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