Medical Case Study 2:
Lighting Up Metals In The Brain
Over the years a lot of evidence has been collected showing subtle differences in trace metals in the brain between people who experience a normal ageing process and people who develop a neurodegenerative disorder like Parkinson’s or Alzheimer’s disease. Synchrotron x-rays provide some sensitive techniques to collect additional information about where the metal ions are distributed in brain tissues and what form they’re in. This will help us to understand if they may be contributing to the disease process, or whether they’re simply a by-product of other processes taking place.
How do you set about looking at the presence of these metals in the tissues?
The concentrations of transition metal ions that are present in the human brain are a very small proportion of the tissue, so we need a sensitive tool to detect them, and one that can allow us to specifically identify the individual elements. If we are looking for iron, which is the most abundant of the transition metals in the brain, we can excite fluorescence from that ion by using an x-ray with sufficiently high energy. What we do at Diamond is have an incoming beam containing a lot of x-rays with the correct energy to excite fluorescence from the metal ions of interest. We are able to focus the beam right down to a very small spot so we can make a map of the tissue based entirely on the distribution of those metal ions.
What have you found so far? Is there a localisation of these metals and if so, where are they?
What we are looking for are subtle changes in metals that are normally present in the brain anyway. It is important to recognise that metals like iron and copper and zinc play an essential role in normal metabolism and they are used for an extremely wide range of processes, so to find them there is perfectly normal. What we’re looking for are differences in the distribution, the concentration and the local environment in which the metals are being used and stored. Also whether we can relate any of these observations to images obtained with scanning technologies that we can use in-vivo as well as in-vitro, such as MRI scanning. The synchrotron is giving us more detailed information than we could have practically obtained from other techniques, and in addition to our studies of iron, we’ve also been able to see in recent analysis the involvement of a range of transition metals associated with certain cells and disease-associated protein deposits. Our work is contributing to existing information, building up a more detailed picture of what’s there.
And is there a hope that further understanding, or being able to visualise this could help earlier treatment of these diseases or what are the possible applications with this knowledge?
At the moment, there are several leads to suggest that changes in the metal ion distribution and form may be taking place significantly in advance of the observation of clinical symptoms. We know, for example, that the hippocampus in Alzheimer’s disease is shrinking (atrophying); that there is significant cell loss in that region that can be observed before somebody is presenting with the full clinical symptoms of Alzheimer’s disease. If certain metal ions contribute to that cell loss and they are part of the mechanism for the cell death, then being able to detect these chemical changes and observe them at an earlier stage, might allow for future treatments to be introduced at a stage before there has been too much atrophy.