23 February 2006
Engineers have found a way to pinpoint and identify the tiny iron oxide particles associated with Alzheimer's and other neurodegenerative diseases in the brain. The technique is likely to accelerate research on the cause of the diseases and could lead to the first diagnostic procedure for Alzheimer's in patients while they are alive. "We're the first to be able to tell you both the location of the particles and what kind of particles they are," said Mark Davidson, a University of Florida engineer in UF's materials science and engineering department. Davidson and collaborators at UF and Keele University in England have published at least four articles on their research in scholarly journals. Their latest article has been accepted for publication in the Journal of Alzheimer's Disease.
Alzheimer's, Huntington's and Parkinson's diseases affect millions of Americans and cost billions of dollars annually for patient treatment and care. Alzheimer's is the most common of the three, afflicting 4.5 million Americans, with numbers projected to grow as the baby boomers age, according to the Alzheimer's Association. The diseases share some potential symptoms, including physical impairments and dementia. Although Huntington's is caused by a genetic disorder, little is understood about precisely how Huntington's, Alzheimer's and Parkinson's wreak havoc in the brain. However, medical researchers have long known that afflicted regions tend to contain unusually high concentrations of iron oxide and other iron-containing particles. This observation is complicated by the fact that healthy brains also contain iron – indeed, iron is essential for normal brain function. Traditional methods for studying the properties of "bad iron" tied to neurodegenerative diseases involve staining tissue sections to reveal the location of the iron, or extracting the particles. But these approaches reveal neither the specific iron compounds present nor the relationship of those compounds to specific structures within the tissue. Electron microscopes don't work either because their tight resolution makes it impossible to search enough area to find the iron. "It would take you a career to look at one piece of tissue," Davidson said.
To solve the problem, Davidson and Chris Batich, a professor of materials science and engineering, along with Albina Mikhaylova, Jon Dobson and Joanna Collingwood of Keele University, turned to an unlikely facility: the synchrotron at the U.S. Department of Energy's Argonne National Laboratory near Chicago. The synchrotron is an electron accelerator that produces the most powerful X-rays in the nation. Also known as the Advanced Photon Source, it is usually used for basic science experiments in high-energy physics. But the UF researchers crafted a system of mirrors and lenses that taps one of the cyclotron's 35 "beam lines," or X-ray sources, for the new purpose of analyzing brain tissue. The results are impressive. Whereas an electron microscope can examine tissue one micron, or one thousandth of a centimeter, the new device can look at tissue two or three hundred microns in size. If it locates a particle, it then uses traditional spectroscopic methods to zoom in and determine what sort of iron the particle happens to be. "It's the equivalent of being up in an airplane, looking at the city of Tampa, and telling you whether there is a penny there or not," Davidson said. "And then once we zoom in, we can tell you what kind of penny it is." So little is understood about the role of iron in neurodegenerative diseases today that it's not even clear whether the iron is a symptom or a cause, Batich said. The UF technique may help by giving researchers a clearer view of the problem. "The basic idea is, if you understand the mechanism, you can understand ways to try to treat the disease," he said. But the UF technique could also have clinical value. Davidson said that the group is planning to do experiments that could one day lead to using magnetic resonance imaging, or MRI, to highlight damaging iron in patients' brains. "If we can adjust the MRI to look for specific iron compounds related to Alzheimer's we may be able to provide a technique for early diagnosis before clinical symptoms appear. The major advantage of this is that most treatments currently in development rely on early detection to slow or halt progression of the disease, as they cannot reverse it," he said.