Discovery prompts rethink on metals and Alzheimer's disease

Discovery prompts rethink on metals and Alzheimer's disease

Researchers at the University of Melbourne have discovered that a protein involved in the progression of Alzheimer's disease also has properties that could be helpful for human health.

The discovery helps researchers better understand the complicated brain chemistry behind the development of Alzheimer's disease, a condition that affects hundreds of thousands of Australians.

An international team of researchers, led by Dr Simon Drew at the University of Melbourne and Prof Wojciech Bal at the Polish Academy of Sciences, has revealed that a shorter form of a protein called beta amyloid, may act as a sponge that safely binds a metal that can damage brain tissue when it's in excess.

Researchers have been intensely interested in the role of beta-amyloid in the development of Alzheimer's disease. This is because clumps of the protein are formed in brains of people with the illness.

In the late 1990s, high levels of copper were discovered within these clumps. Copper is essential to health, but too much can produce harmful . Many scientists began to suspect that this copper might be contributing to the disease. They found that beta-amyloid can bind to copper indiscriminately and allow it to produce these damaging free radicals.

Closer analysis of beta amyloid protein has revealed different sizes. A good proportion of beta amyloid is missing the first three links at the start of the protein's chain-like structure.

"This short form has been overlooked by most researchers since the composition of beta amyloid was first identified 30 years ago," Dr Simon Drew explains.

"We know that the shorter form of beta amyloid is present in the diseased brain, but we now know that it is abundant in healthy brains as well.

"The small change in length makes a huge difference to its copper binding properties. We found that the short form of the protein is capable of binding copper at least 1000 times stronger than the longer forms. It also wraps around the metal in a way that prevents it from producing free radicals.

"Given these properties and its relative abundance, we can speculate this type of beta amyloid is protective. It's very different from the current view of how beta amyloid interacts with biological copper."

So far, therapies aimed at lowering the production of beta amyloid have shown only a modest ability to slow cognitive decline and the number of people affected by the Alzheimer's disease continues to grow.

Dr Drew and the team from Poland are now working to develop a method for identifying the copper-bound form of the short beta amyloid in the body.

This will enable them to screen how much copper it holds in the brain, whether it safely escorts the copper from one place to another, and how this may change in ageing and disease.

"If a beneficial role in copper balance can be established, it's still possible to have too much of a good thing," Dr Drew said.

"As the amount of in the brain increases during Alzheimer's disease, the shorter form can also clump together and this may interfere with its normal function. Higher levels of the short form may further enable it to soak up from other places where it is needed. It could be a Jekyll and Hyde scenario."

Dr Drew's research was published in Angewandte Chemie.

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Journal information: Angewandte Chemie

Citation: Discovery prompts rethink on metals and Alzheimer's disease (2015, July 30) retrieved 23 July 2019 from
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Jul 30, 2015
I realize that medical research has it's aha moments, and there are many ups and downs along the way to finding any cure, but everything I thought I had learned is destroyed by this article. Yes, I have long believed the beta amyloid protein coats injured parts of the brain and is protective in nature. But where this article stops, is in not identifying the Tau protein, which is believed to hide under the amyloid coating and entangle with neurons, killing brain cells along the way, thus the deteriorization during the Alzheimer's journey. I have always found it interesting how proteins are essential for our physical survival, but how proteins can go rogue and cause cancer and many other horrible diseases. I believe if they actually find a way to control these rogue proteins, there will be far reaching positive implications for medicine.

Jul 30, 2015
To clarify my interest in this, I watched my Mom die from this horrible disease, Alzheimer's. I am now watching my wife care for her Mom, with the same. And 8 months ago, my neurologist diagnosed me with early onset, originating from brain damage due to strokes. I spent countless hours researching over this lengthy period of time, learning as much as I could about Dementia/Alzheimer's, because I believe knowledge is power. While still able to do so, I wrote most likely, my final book on the subject, titled "Painful Avoidance". It is available on Amazon in both Kindle and print formats. The purpose of this book is to hopefully improve understanding between caregiver and patient, and shed some light on this disease, and how best to handle certain situations.

Jul 30, 2015
There was an older article here several months ago which showed low copper allowed the NMDA receptor to become overstimulated leading to synapse death but, can't find it at moment... There are some 200 enzymes which need or utilise copper in various ways and some 150 which utilise Zinc, both those metals have a love/hate relationship and the whole area of metaloid enzymes/proteins is not just not well understood but appears to be casually avoided with the research presumption the bulk of treatments for a great many conditions should not include metals... Eg Look at the new drugs for host of conditions - devoid of metals, yet human biology conversely shows evidence of embracing metals in many useful ways...

When one also looks at definitions of enzymes vs catalysts and the issue with proteins then research becomes even more complex ie All enzymes are proteins but not all proteins are (yet) observed to act enzymatically & Non-protein catalysts well, another story...

Jul 30, 2015
I agree with Mike. Zinc and Copper are mutually antagonistic. Excessive copper leads to low zinc as well as the opposite. I read a recent article that possibly showed that the plaque build up was the end stage of the disease not the beginning. Intriguing. This same article seemed to show that curcumin enters the neuron protecting it from being damaged which stopped the build of the plaque. The more we learn the less we know.

Jul 31, 2015
Interesting oddity re combative/antagonistic absorption re Copper/Zinc is that both are affected negatively by Iron, in that high iron intake antagonizes Copper/Zinc absorption. The odd thing, which the vast bulk of doctors are totally unaware of - especially when prescribing iron supplements to those diagnosed with anemia is that the mechanism for humans metabolising iron is that it occurs through three proteins/enzymes ie Ceruloplasmin, hephaestin & other Ferroxidases the latter of which contains afaik copper within typical porphyrin ring.

In Australia Iron is very common plentiful in most foods but, copper is extremely low, potential conclusion is prescribing iron re anemia might make things worse in the long term with the implication that, unless someone has Wilson's disease, increasing copper ostensibly, to improve functionality of Ferroxidases, may be the best mechanism to combat anemia with the added benefit of raising our copper intake Eg treating skin conditions...

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