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Studying ferritin: ‘we hope this will eventually give more insight into Alzheimer's’

Exactly how Alzheimer's disease develops is not well understood, but an imbalance of iron in the brain might just play a role. Martina Huber of the Leiden Institute of Physics studied the magnetic properties of ferritin, which is responsible for iron storage in the brain. For this, she managed to combine two techniques. 'We had to bring together the expertise of various disciplines and I am proud that we succeeded.'

‘Alzheimer's is a complex condition and we are only studying a small part,’ Huber says. Yet it forms the main motivation for her research group. ‘We know that in individuals with Alzheimer's, there is too much iron in certain parts of the brain. We want to understand that better.’ About one in five Dutch people develop dementia and Alzheimer's is by far the most common form. In this disease, nerve cells in the brain break down, causing patients to have difficulty with their memory and everyday actions. A cure does not exist.

How does a physicist investigate Alzheimer's?

In a recent publication, the scientist combines two techniques mainly used in physics. ‘With a so-called SQUID-detector, we measure the magnetisation. That indicates the extent to which a material responds to a magnetic field. We complement that with electron paramagnetic resonance (EPR) measurements. In this work, we have done purely fundamental research to understand ferritin, but our group also deploys these techniques for biological samples such as samples from the brain.’

‘There are all kinds of theories about Alzheimer's, but the answer is far away.'

EPR exploits a very special quantum property of subatomic particles: spin. You can imagine this as a particle spinning by itself. When it has a charge, it creates a very small magnetic field and interacts with other particles in the environment. Researchers can measure that with EPR, Huber explains. ‘We do the most sensitive EPR measurements in the whole of the Netherlands. We can even study single crystals and that gives a lot of information about a system.’

A ferritine particle with a protein shell and iron core.

Iron storage in the brain

Iron in the human body is stored in the protein ferritin. That is a spherical nanoparticle made of two types of proteins that interlock like the black and white surfaces on a football. They form a protein shell with a completely enclosed cavity inside. Iron ions can enter through the shell and lose an electron in the process. At 2000 ions, the cavity is full and the iron forms an oxide that has a magnetic moment. This can be studied with EPR. ‘Sometimes we work with brain material, but not in this case. First we wanted to understand ferritin in its pure form, produced in the lab. That's tricky enough.’

Huber brought together two fields of expertise in her research and that was certainly a challenge she says. ‘To interpret the data properly, we asked for help from a researcher studying nanomaterials in palaeogeology. The history of the Earth, in other words. We clearly have completely different backgrounds, but we managed to formulate a common theory. It was very interesting to learn more about each other's fields. I picked it up better than I expected to be honest.'

One step closer

‘There are all kinds of theories about Alzheimer's, but the road is long and the answer far away. A lot of research is still needed,’ Huber mentions. ‘In previous research, we showed that by combining magnetometry and EPR, we can learn more about the iron composition in the brain. This recent publication shows that we can also map the magnetic properties of ferritin. That's a great step.’ She shrugs: ‘Of course, we hope that our research will eventually contribute to a better understanding of Alzheimer's, although it could just as easily be a dead end. The physics behind it is interesting in any case, so the research is fun either way.'

The research about the magnetic properties of ferritin was published in the scientific journal Physical Chemistry Chemical Physics under the title In-depth magnetometry and EPR analysis of the spin structure of human-liver ferritin: from DC to 9 GHz.

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