September 28, 2017
Dr. Joanna Collingwood, Ph.D., a physicist at Warwick University in Coventry, England, leads a research team probing whether the iron particles found in the brain contribute to the breakdown of nerve cells in Alzheimer’s disease. They use an advanced technology called a synchrotron, which is 10,000 times more powerful than a traditional microscope, to map and study the interaction between iron particles and the beta-amyloid plaques that build up in Alzheimer’s.
- Iron is being studied as a possible factor in the breakdown of brain nerve cells
- Particles of iron have been discovered in beta-amyloid plaque
- Research is focused on whether beta-amyloid plaques are causing the iron to become harmful or whether they are protecting the rest of the brain
Being Patient: What role do metals play in the body and why are they important in the study of diseases like Alzheimer’s?
Joanna Collingwood: There are metals that we take in from our diet like calcium, zinc and copper, which are essential for the functioning of a normal, healthy brain. They form important parts of proteins and enzymes throughout the body. Storing iron in this form makes it available for lots of different processes, but also ensures it’s not free to take part in other chemical reactions. Iron can quickly and easily get involved in the formation of free radicals, which can damage the membranes of brain cells.
Being Patient: What have you found out about the interaction between iron and beta-amyloid?
Joanna Collingwood: We use very intense X-ray beams to build maps of where metals are distributed in areas of the brain. When we looked at beta-amyloid plaques from the brains of people who had Alzheimer’s disease, we saw that there were particles of iron oxide in them. The iron that we saw in the beta-amyloid plaques wasn’t the normal form of iron oxide found in the body, which is called iron III. We found that some of the iron was in a chemically reduced form called iron II.
In the lab, when we put an iron III into a solution that matches the typical pH level in the human body, it would normally stabilize in that form. If we introduce beta-amyloid protein at the point where it’s just starting to stick together, a fraction of the iron becomes iron II. This form is strongly implicated in the formation of free radicals. So, we think that iron in the presence of beta-amyloid will be chemically reduced more than what is normal. Iron II could become a source for the over-production of free radicals. That’s what we’re trying to protect against in the body normally. This is the oxidative stress hypothesis for neurodegenerative diseases like dementia. It looks at the breakdown of nerve cells that happens as a result of damage caused by free radicals. Iron could be a driver of the kind of damage we see in these diseases.
Being Patient: If you’re a drug company or clinical researcher, how will this affect the search for a cure?
Joanna Collingwood: We’re trying to establish whether the interaction between beta-amyloid and iron can explain some of the toxicity associated with the build-up of beta-amyloid. We know that in the places where beta-amyloid builds up there’s evidence of toxicity in the tissues, but is the beta-amyloid the source of toxicity, or is the reduction of the iron a factor in that? The beta-amyloid could even be protective where iron and other metals are embedded within the plaques. They may isolate the metals, blocking chemical reactions from taking place in the tissue that lead to cell damage. If we dissolve those plaques we could release those metals into the tissue and give the brain more work to do to avoid the free radical damage. We don’t yet know if metals embedded in beta-amyloid plaques continue to drive the formation of free radicals. There are many factors in neurodegeneration, but we can’t fully understand the role of beta amyloid without taking into account the effect it has on the metals in the brain.