For over 40 years scientists have known that aluminum deposits are found in the brains of Alzheimer’s patients at more than twice the level of other people. They still are not able, however, to find the specific link between the exposure to aluminum and neurodegenerative diseases so they are looking at other metals to see if they can offer a clue.
A cooperative study in 2007, led by Emory University and including several other institutions such as the University of Georgia, found that metal ions cause toxicity in brain cells because they bind themselves to amyloid fibrils. Amyloid fibrils are linked to the development of neurodegenerative diseases such as Alzheimer’s and Parkinson’s.
The study, published in the Proceedings of the National Academy of Sciences, reports that ions from copper, zinc and iron are found naturally in the brain, and produce an electrical charge by gaining or losing one or more electrons. Metal ions, especially copper, bind to amyloid in several different and specific ways, but researchers have found that only one way can produce toxicity. Amyloids, typically hard, waxy deposits containing mostly protein are found in body tissue.
“There is increasing evidence that links the ions in the brain to amyloid assembly and the Alzheimer’s disease,” says David Lynn, Emory chair of chemistry and principal investigator of the study. Although little is known as to how these amyloid fibrils are formed, the results from the study suggest that the exact way amyloid binds to copper ions affects the structure of the fibers, the rate in which they multiply, and what sort of effect they may have on surrounding neurons.
“Not all amyloid fibrils are toxic,” says Lynn. “Amyloid is made of proteins, and proteins are normally fold into beautiful structures. However, for whatever reason, some misfold, and the resulting misfolded structures, are also beautiful – but sticky. They stick to themselves and then propagate to form fibrils, but only some of the fibrils turn out to be toxic.”
Normally folded proteins decompose shortly after being produced. Abnormal folds accumulate and interfere with the brain’s structure and function over a period of time. The brains of patients who suffered from Alzheimer’s disease showed an unusual amount of sticky amyloid fibrils.
The scientists were able to determine what the effect on brain cells was according to the activity influencing the assembly. They could determine the toxicity of the whole amyloid fibrils by examining the chemical properties of individual units of amino acid’s when binding with metal.
“We showed that the activity of this minimal unit actually replicates the activity of the whole fibril on the neuronal cell. And it does so by binding the metal in a specific way,” says Lynn. They also found that several distinct types of structures could be assembled from individual units of amino acids. “We found that we could build lots of different types of structures with an individual unit: fettuccine-shaped structures, tubes, vesicles, and so on, not just fibers. And this is remarkable,” says Lynn.
“Like many scientific findings, we know about amyloid because of the diseases it’s associated with rather than because of its benefits,” says Lynn. “However, researchers are also finding situations in which amyloid is beneficial, such as in long-term memory and synapse maintenance in the marine snail.”
“Our findings now lead us to ask what other types of structures these individual units can make, what exactly happens when the units bind to one another, and whether these individual units are important to neurodegenerative diseases or whether the entire fibril must be involved,” says Lynn.
About the author:
Ron White is a two-time U.S.A. Memory Champion and memory training expert. As a memory keynote speaker he travels the world to speak before large groups or small company seminars, demonstrating his memory skills and teaching others how to improve their memory, and how important a good memory is in all phases of your life. His CDs and memory products are also available online at BrainAthlete.com.
Wikipedia — Neurodegeneration: http://en.wikipedia.org/wiki/Neurodegeneration
Center for Neurodegenerative Disease — Emery-led Study links Alzheimer’s to Lead: http://www.emory.edu/news/Releases/Metals_to_Alzheimers1186774207.html
Proceedings of the National Academy of Sciences, Early Edition online during the week of Aug. 6-10, and in the print edition Aug. 14, 2007