Iron Contributes to Plaques in Alzheimer's Disease

There is a very close link between elevated levels of iron in the brain and the enhanced production of the amyloid precursor protein (APP) in Alzheimer's disease.

This protein (APP) breaks down into a peptide that makes up the destructive amyloid plaques that are characteristic of Alzheimer's disease (AD). An abundance of iron in brain cells results in an abundance of APP, and its destructive peptide residue.

In a study, carried out at Massachusetts General Hospital, (Boston, MA, USA), scientists were able to identify important molecules in the system of checks and balances used to regulate iron in brain cells. Iron-regulating protein 1 (IRP1), is the special molecule that attaches to the messenger ribonucleic acid (mRNA) that is key to the production of APP. The team had previously reported that, if there is too little iron, fewer APP molecules are made available to help escort iron out. As a result, iron accumulates, and the process begins again in a feedback loop. When there is less iron in the brain cell, IRP1 is more likely to link up with the RNA, which prevents the production of APP. When there is abundant iron present, IRP1 does not connect to the RNA, and APP production becomes excessive.

The finding that steady-state levels of intracellular APP are tightly regulated by iron is consistent with the preliminary clinical studies showing that copper and iron chelation may therapeutically reduce APP levels and lower Aβ peptide product in brain subregions. Inhibition of APP translation mediated through the APP 5′-untranslated region (UTR) provides another mechanism by which chelators could be therapeutic agents for the treatment of AD patients

Jack T. Rogers, Ph.D., the senior author, said, "these findings lay the foundation for the development of new therapies that will slow or stop the negative effects of iron buildup in patients with the progressive neurodegenerative disease, symptoms of which include memory loss, impaired judgment, and disorientation and personality changes." The study was published on October 2010, in the Journal of Biochemistry.

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