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Alzheimer's May Be Tied to Lack of Iron

 

Iron deficiency, the world's leading nutrient shortfall, may play a role in brain-degrading diseases like Alzheimer's, a new study has found.

Human brain cells deprived of a key form of iron, called heme, develop damage similar to that in cells with Alzheimer's. One mechanism for the harm may be oxidative stress, or the rusting of neurons, say the researchers, who report their findings this week in the Proceedings of the National Academy of Sciences .

Oxidative stress has previously been linked to Alzheimer's, although how important it is in the development of the disease isn't understood.

Between 4 billion and 5 billion people -- as much as 80 percent of the world's population -- may be iron deficient, according to the World Health Organization. Roughly 30 percent of people suffer from anemia, a critical lack of the nutrient in their blood.

Heme deficiency can be caused by too little vitamin B6, as well as by exposure to aluminum and other toxic metals. It is a frequent companion of aging, menopause, and pregnancy.

Alzheimer's disease now affects at least 4 million Americans. That number could top 14 million or more by 2050, according to the Alzheimer's Association.

In the new study, Oakland, Calif., researchers examined two types of human brain tumor cells, neuroblastomas and astrocytomas, as well as neurons from rats. To produce iron deficiency, they treated the tissue with a compound that significantly suppresses heme synthesis.

The result: heme-deficient brain cells had less activity in their mitochondria, which are cellular energy factories. They also made more of an enzyme that generates nitric oxide, a molecule that can cause oxidative stress, and showed anomalies in their balance of iron and zinc.

Normally, neuroblastoma and astrocytoma cells will divide perpetually. But without sufficient heme, they died when pushed to multiply.

Hani Atamna, a scientist at Children's Hospital Oakland Research Institute and a co-author of the study, says many of these changes mimic what happens to the brain cells of people with Alzheimer's disease. Although the researchers experimented on cancer cells, which are by definition awry, they produced similar effects by blocking heme in tissue from normal rat brains, too.

Atamna and his colleagues now plan to study the effects of iron deficiency on the brains of live animals. And they are comparing tissue samples from people with Alzheimer's to those without dementia, to further explore potential problems with the metal.

Many scientists believe Alzheimer's is caused by thickets of a protein called amyloid-beta. Atamna's group couldn't see if low iron promoted these plaques, but they're working on studies that may answer the question, he says. The researchers are also interested in following people over time to see how fluctuations in iron may affect their brain health.

Dr. David Bennett, director of the Rush Alzheimer's Disease Center in Chicago, says he's not aware of any population studies linking low iron to dementia. But other researchers have found a link between high iron levels in the brain and Alzheimer's, he says.

What that means isn't clear, Bennett adds, since the metal could be sitting on the sidelines of cell activity, leading to a deficiency.

As a result, Bennett is cautious not to overstate the importance of the latest study, calling it "just another piece of data that would support" looking into a possible role of iron in brain disease.



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