Australasian Science: Australia's authority on science since 1938

Excess Iron Linked to Alzheimer’s and Parkinson’s

By Stephen Luntz

is excess iron a cause or an effect?

Both Alzheimer’s and Parkinson’s disease have been linked to failures in a protein that normally removes excess iron from brain cells. Many obstacles exist to treatment, but the discovery holds out the tantalising prospect of addressing the two most devastating neurological diseases in one go.

Both Alzheimer’s and Parkinson’s diseases are associated with iron accumulation in the brain, but there has been debate about whether this is a cause or an effect. Alzheimer’s is also associated with the tau protein, and there is recent evidence this may be more important than the more famous amyloid beta plaques (AS, March 2012, p.6).

Prof Ashley Bush of the Mental Health Research Institute co-authored a paper in Nature Medicine raising the possibility that the problem may not be too much tau, but rather the transformation of tau from its soluble to its insoluble form.

In Alzheimer’s disease tau is observed in neurofibrillary tangles. Less noticed is that this is associated with a reduction in soluble tau. A similar fall in tau is observed in Parkinson’s disease.

Now Bush has shown that one of the functions of tau in a healthy brain is to transport the protein APP to the surface of nerve cells, where it can pump out excess iron. A shortage of soluble tau prevents APP doing its job, allowing iron to build up.

“All cells use bellows to remove iron and put it outside the cell,” Bush says. “Iron has to be moved in such a way that it doesn’t rust”. Tau has previously been linked to microtubule activity, but Bush calls this “pretty non-specific”.

Bush has shown that damaged brain cells treated with drugs to remove excess iron can recover, but he says that a suitable drug does not exist. “There are drugs that remove iron from all tissues, usually used for conditions with iron overload,” he says. However, such a drug would need to cross the blood–brain barrier, which not all do, and even then it might cause an unhealthy drop in iron elsewhere in the body.

Bush has tested clioquinol, a drug that specifically targets cells with high metal concentrations, and says this showed promise in mice and in vitro brain cells. He considers this work a good proof-of-principle, but says it will be a long time before anything is on the market.

Clioquinol has previously shown promise against Alzheimer’s disease, but this was attributed to its effectiveness at removing copper and zinc.