Function found for Alzheimer’s protein APP

A new study reveals that when amyloid precursor protein (APP) fails to convert iron from an unsafe form to a safe one for transport or storage, it leads to rise in iron levels inside neurons mount to toxic levels and eventually causes Alzheimer’s disease.

The study is reported by Ashley Bush of The Mental Health Research Institute, University of Melbourne. in the issue of Cell.

Some years ago, the researchers discovered that the RNA template for the APP protein includes an iron-responsive element. When iron levels rise, cells ramp up their APP production.

But amyloid in and of itself doesn’t really explain what goes wrong in the Alzheimer’s brain. “There has been a lot of attention on amyloid, but it seems it is not a simple matter of amyloid as the sole culprit,” Bush said. For one thing, trials of drugs designed to target and clear amyloid plaques haven’t worked as intended.

In fact, the disease is also complicated by high concentrations of metals, including iron that builds up inside neurons and zinc that accumulates within the amyloid plaques outside of those brain cells.

After 10 years of work, it appears Bush’s and Roger’s teams have connected the dots from the abnormal exchange of zinc to amyloid pathology and iron accumulation in Alzheimer’s disease. “It’s a sequence of dominoes falling onto each other,” Bush said.

Based on the new evidence, the researchers propose that elevated iron in the Alzheimer’s brain summons further APP production. But that APP — generated for the purpose of exporting iron — gets disabled by high levels of zinc that dissociate from the amlyoid plaques.

The findings suggest that zinc may be an ideal target in the fight against Alzheimer’s disease, the researchers say.

Source: Cell Press, USA



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