Wednesday, 8 April 2015

Focusing ‘big science’ on the microscopic detail of Alzheimer’s disease

Physicists, chemists and material scientists have developed an army of high-tech tools to probe the chemical and magnetic properties of materials at length scales of about 1/10000th of the width of a human hair (i.e. the nanoscale). In particular, x-ray techniques have evolved that can study such materials in minute detail and in non-destructive ways.
Chemical map of an aggregate of the Alzheimer’s disease peptide amyloid-beta (blue), and accumulated iron (red), obtained using the synchrotron x-ray technique known as spectromicroscoppy
Our research in this area is concerned with applying some of these techniques, previously exclusive to the realms of physics and chemistry, to the study of biological materials. These experiments require the use of synchrotrons such as the Diamond Light source in Oxfordshire, which are giant donut-shaped x-ray machines that can generate intense beams of x-ray light 10 billion times brighter than the sun. Other important requirements of synchrotrons are the ability to focus the light into microscopic probes, and the production of light with a full spectrum of wavelengths (just like the light from the sun).

Combining these properties enables us to perform both microscopy (creating nanoscale images of our samples) and spectroscopy (measuring a property of our sample as the x-ray wavelength is scanned). In fact, the latest state-of-the-art instruments enable us to combine these techniques into a process known as spectromicroscopy. Here we obtain a set of nanoscale images at many different x-ray wavelengths. This enables us to measure the distribution of the chemical and magnetic properties of our sample across regions as small as a few nanometers. It is therefore possible to study how different materials interact at the length scales of relevance to biology.

In our work we are interested in how a specific biological peptide known as amyloid-beta, which is implicated in the pathology of Alzheimer’s and other diseases, interacts with different forms of iron that occur naturally in our bodies. Using spectromicroscopy we were have been able to obtain chemical maps (such as the one shown below) that reveal the accumulation of iron (shown as red) within aggregates of the peptide (shown as blue) when incubated together in the laboratory. Combined with x-ray spectroscopy we were also able to show that the iron was slowly converted from a non-toxic form known as ferric iron, to a potentially neurotoxic ferrous form, following prolonged interaction with the peptide.

Alzheimer's disease is a major condition effecting increasingly large numbers of people, both old and young. The importance of this work is that it demonstrates a potential mechanism for the damage that occurs in the brain during Alzheimer’s disease. Using the same x-ray techniques we have now begun to study specimens of human brain tissue donated by Alzheimer’s patients, and can see interesting parallels in the nature of iron in these tissue samples compared to those we obtain in the lab. Understanding the role of iron in diseases such as Alzheimer’s is important for both early diagnosis using MRI scans, and for potential new treatments that could use the accumulated iron as a chemical target for drugs to attack.

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