Iron in the brains of Parkinson's disease sufferers
The accumulation of metals in brain tissue has frequently been associated with neurological disorders - Alzheimer's disease is linked to aluminium, Wilson's disease to copper and Hallervorden-Spatz disease to iron. It has been known for some time that sufferers of Parkinson's disease also have abnormally high levels of iron in the brain. Paul Griffiths of Newcastle General Hospital Department of Neuroradiology, in collaboration with Barry Dobson and Gareth Jones at Daresbury Laboratory, have used the SRS to investigate how iron is stored in the brain in both healthy and Parkinson's diseased tissue. Now, for the first time, definite conclusions have been drawn about the method of iron storage.
Iron is stored throughout the brain, accumulating rapidly during adolescence and early adulthood. The areas containing most iron are at the base of the brain - the substantia nigra and the globus pallidus - and these areas are also thought to be affected most in degenerative diseases. The presence of iron is perfectly normal; a healthy adult brain might contain 50 mg of iron per gram of tissue. However, in Parkinson's sufferers, this figure can rise to 250 mg per gram of tissue. Examining tissue from healthy brains and from Parkinson's sufferers, shows the similarities and differences in the iron deposits.
A common method of iron storage in the body is via a protein called ferritin. Ferritin is a large protein, like a molecular football, that can hold 30 or 40 iron atoms inside. The iron is inert when it is stored inside the ferritin. A technique called X-ray Absorption Fine Structure (or XAFS) Spectroscopy has been used to study the brain tissue. XAFS 'homes in' on particular atoms in a sample, and then identifies the position and type of their nearest neighbours. Using this technique the environment of the iron atoms in the brain can be studied in detail, clearly showing the signature of ferritin in both healthy and diseased tissue. The brain iron can now be positively identified as ferritin.
In addition to characterising the iron deposits with XAFS, the core centres can be imaged using cryo electron microscopy.
Ferritin cores in the brain tissue show up clearly as dark spots on the image. The microscopy not only shows the location of the cores, but also indicates their density. Here a clear difference is seen between normal and Parkinson's tissue, with the ferritin 'footballs' in diseased brains being more heavily loaded with iron.
The role of iron in Parkinson's disease is not yet fully understood. However, these experiments have given the first conclusive results of the method of iron storage in the brain. This knowledge may improve our understanding of the degenerative processes involved in Parkinson's disease.
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