08 October 2013

Is excess iron one of the causes of Alzheimer's disease?

The cause of Alzheimer's disease may be the accumulation of iron in the brain

LifeSciencesToday based on materials from the University of California – Los Angeles:
UCLA study suggests iron is at core of Alzheimer's diseaseAlzheimer's disease has proven to be a difficult opponent.

After all, the number one factor in the development of this neurodegenerative disease is aging, and we cannot stop it.

According to most scientists, this disease is caused by two proteins – tau protein and beta-amyloid. As they age, the researchers believe, these proteins either disrupt interneuronal signaling or simply kill nerve cells.

Scientists at the University of California at Los Angeles (UCLA) are sure that there is a third reason – the accumulation of iron.

Psychiatry professor George Bartzokis, MD, from the Semel Institute for Neuroscience and Human Behavior at UCLA, senior author of the study, and his colleagues studied two brain regions of patients with Alzheimer's disease. They compared the hippocampus, which is known to be affected already at the beginning of the disease, and the thalamus, an area that usually remains intact until its last stages. Using sophisticated brain imaging techniques, they found an increase in iron levels in the hippocampus and proved that it is associated with tissue damage in this area. There was no increase in the level of iron in the thalamus.

Although in most cases scientists focus their attention on the formation of neurofibrillary tangles of tau protein or beta-amyloid plaques, Professor Bartzokis has long argued that the "breakdown" happens much "higher". According to him, the destruction of myelin, a fat–like substance covering the nerve fibers of the brain, disrupts interneuronal communication and contributes to the formation of plaques. In turn, amyloid plaques destroy more and more myelin, interrupting the transmission of nerve impulses and leading to cell death and the classic clinical symptoms of Alzheimer's disease.

Myelin is produced by cells called oligodendrocytes. Of all brain cells, oligodendrocytes, along with myelin itself, have the highest iron content, and, according to Professor Bartzokis, indirect evidence has long suggested the possibility that iron levels in the brain may be a risk factor for age-related diseases such as Alzheimer's disease. Although iron is vital for cells to perform their functions, too much of it can contribute to oxidative damage, to which the brain is particularly sensitive.

Co-culture of oligodendrocytes and neurons (photo: Andrew Jarjour / news.bbcimg.co.uk )In the present study, Professor Bartzokis and his colleagues tested their assumption that elevated levels of iron in the tissue cause its destruction, associated with Alzheimer's disease.

Using MRI, which allows measuring the amount of iron in the ferritin protein, they determined its level in brain tissue in 31 patients with Alzheimer's disease and 68 healthy individuals who made up the control group.

In diseases such as Alzheimer's disease, when the cell structure is destroyed, the amount of water in the brain increases, which makes it difficult to detect iron.

"When the tissue is already damaged, it is very difficult to measure the level of iron in it," says Professor Bartzokis. "But the MRI method we used in this study allowed us to determine that an increase in iron levels occurs along with tissue damage. We found that the amount of iron is increased in the hippocampus and this increase is associated with tissue damage in patients with Alzheimer's disease, but not in healthy elderly people – or in the thalamus. Thus, the results show that iron accumulation may indeed be one of the causes of Alzheimer's disease."

But this is not all bad news, adds Professor Bartzokis.

"The accumulation of iron in the brain is influenced by environmental factors, such as the amount of red meat consumed and dietary supplements with iron. In women, the cause of iron accumulation may be a hysterectomy before menopause," explains the scientist.

At the same time, several pharmaceutical companies are currently developing drugs for the treatment of such disorders that chelate and remove iron from tissues. The MRI method may allow doctors to determine who needs such treatment the most.

The study (Raven et al., Increased Iron Levels and Decreased Tissue Integrity in Hippocampus of Alzheimer's Disease Detected in vivo with Magnetic Resonance Imaging) is published in the Journal of Alzheimer's Disease.

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