Visualising Iron in the Human Brain

Whereas iron is important for many life processes, a poor regulation of the iron household, or release of iron from damaged tissue can cause toxic chemical reactions that can even lead to cell death. Thus, too much iron could damage an organism. Iron accumulates in certain brain areas such as the basal ganglia in the ageing human brain, and it is not known why, and how, this iron storage takes place. Many neurodegenerative diseases also go along with an accumulation of iron in the brain, but little is known of the role a poor regulation of iron plays in these diseases. To understand this role, we first need to know the mechanism by which iron accumulates in the brain. Iron in the brain is stored in ferritin proteins, which we can detect using analytical electron microscopy (EM). Here we propose studying brain samples of deceased patients who did not die of neurological diseases, so that we can combine analytical EM, to visualise the iron accumulation at high resolution, with quantitative magnetic resonance imaging to display the iron content in different brain areas, and mass spectrometry to measure the total iron content in these brain areas. This will enable us to study the way iron is stored and to investigate which cell types and which subcellular compartments act as iron stores in the human brain. We further aim to determine the numerical density of ferritin particles and to quantify their size and iron content. Furthermore, we aim to use samples of deceased patients who suffered from Alzheimers disease to detect putative changes in their iron household. We expect that this study will be useful as a reference for future studies on the role of iron dysregulation in neurodegenerative disease. 1

Whereas iron is important for many life processes, a poor regulation of the iron household, or release of iron from damaged tissue can cause toxic chemical reactions that can even lead to cell death. Thus, too much iron could damage an organism. Iron accumulates in certain brain areas such as the basal ganglia in the ageing human brain, and it is not known why, and how, this iron storage takes place. Many neurodegenerative diseases also go along with an accumulation of iron in the brain, but little is known of the role a poor regulation of iron plays in these diseases. To understand this role, we first need to know the mechanism by which iron accumulates in the brain. Iron in the brain is stored in ferritin proteins, which we can detect using analytical electron microscopy (EM). Here we studied brain samples of deceased patients who did not die of neurological diseases, so that we could combine analytical EM, to visualise the iron accumulation at high resolution, with quantitative magnetic resonance imaging to display the iron content in different brain areas, and mass spectrometry to measure the total iron content in these brain areas. This enabled us to study the way iron is stored and to investigate which cell types and which subcellular compartments act as iron stores in the human brain. We further determined the numerical density of ferritin particles and to quantify their size and iron content. Furthermore, we used samples of deceased patients who suffered from Alzheimers disease to detect putative changes in their iron household. We expect that this study will be useful as a reference for future studies on the role of iron dysregulation in neurodegenerative disease