Illuminating Alzheimer's: Research Sheds First-Ever Light on Creatine's Presence in Alzheimer's-Affected Brain Tissues
John Morgan, Science Writer, UW Madison Synchrotron Radiation Center
December 13, 2005
Alzheimer's disease is one of the most hauntingly destructive maladies to wreak havoc on humans. It robs children of parents and spouses of each other--with lifetimes of memories lost forever behind blank stares. But researchers are feverishly plowing toward answers to the many questions that have made Alzheimer's a complex and unsolved degenerative disease and, in some cases, a death sentence.
In a recent article in the Journal of Biological Chemistry a team of Canadian and American scientists reports the first-ever finding of elevated levels of creatine--the newly discovered agent of Alzheimer's--in brain tissue. The article is available pre-press at the Journal of Biological Chemistry's Website (an on-line offering of articles soon to be in the print version of the journal).
"It is the first time anyone has succeeded in detecting creatine directly in situ, in any tissue. The usual methods are to grind up a large amount of tissue and extract it in bulk," explains the paper's lead author, Kathleen Gough, professor of chemistry at the University of Manitoba.
Gough and her colleagues, along with many others in the field, are searching tenaciously for the molecular answers that might someday lead to the end of Alzheimer's disease. Of particular note regarding the current study was the use of infrared spectroscopy as another tool that has contributed to the body of knowledge regarding Alzheimer's.
"It's the first time that we've discovered creatine in Alzheimer's disease samples that didn't appear in control samples. Nobody has ever seen this before," explains Dr. Robert Julian, an expert in infrared spectroscopy at the University of Wisconsin, Synchrotron Radiation Center, the light source utilized for this project.
The key to using infrared, the researchers explain, is that it is relatively unobtrusive as compared to normal laboratory protocols used to study brain tissues, thus keeping the samples closer to being "pristine."
"Due to its small size and great solubility, creatine dissolves and would be washed away under normal tissue preparation protocols for staining. Step one in any staining process is to soak a tissue sample in an aqueous solution of formaldehyde, called formalin. This 'fixes' the proteins in place, but also washes out the small, soluble metabolites like creatine," explains Gough. "What we do is prepare the tissue without any treatment, and we look at unfixed, flash frozen tissue-nothing added or removed, except water."
Thus while the use of synchrotron radiation, a traditionally physics-focused tool for discovery, to study Alzheimer's has surprised some, it may be this application that could one day turn the tide on Alzheimer's Disease.
"That's where all of this is going ultimately-is to try and find a cure," explains Julian.
Yet researchers stress that while this information sheds more light on a troubling disease and might possibly lead to improved treatment, the term "cure" simply cannot be used yet.
"It could be really important," concludes Gough. "It seems that there is an overlooked aspect of energy disturbance in Alzheimer's disease, and maybe in other diseases. We don't know. I am really excited by this finding. I don't know where it will lead and I do realize that it could be the most important contribution of my scientific career. But as to the detailed explanation of why it is there - the jury is still out."
The figure includes spectra of creatine in tissue (red), ordinary tissue (blue), and pure creatine (green).
The image shows a hippocampus with the location of the creatine microcrystals located with the blue peaks. The intensity of a blue peak corresponds to the intensity of the Infrared signal.
Elevated levels of creatine detected in APP transgenic mice and Alzeimer disease brain tissue . Meghan Gallant, Margaret Rak, Adriana Szeghalmi, Marc R. Del Bigio, David Westaway, Jin Yang, Robert Julian, and Kathleen M. Gough. JBC Papers in Press published on November 2, 2005.
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