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Health screenings have become a routine part of our wellness regime. Mammograms, pap smears, colonoscopies, blood tests; all provide screening tools that enable doctors to detect and treat disease during its early stage. Now, scientists working to unlock the mystery of Alzheimer's disease envision a screening that might one day detect the presence of this progressive brain disorder long before it causes the memory to unravel.

The question two researchers at the University of Tennessee Health Science Center (UTHSC) are seeking to answer is whether minute changes in the brain's white matter can be detected early in the disease process of Alzheimer's. To study this question, neurologist Alexander P. Auchus, MD, and research associate Juebin Huang, MD, PhD, are using diffusion tensor imaging (DTI), a variation of MRI that allows scientists to study connections between different brain areas. But instead of examining the brain's cortical gray matter, the researchers are using DTI to examine structural changes in the brain's white matter.

MRIs have long given neurologists valuable information about the health of the brain, since such scans reveal major anatomical features of the brain's gray matter and can offer subtle clues of brain structures gone awry. But with DTI, researchers are better able to examine and understand the brain's micro-architecture. Over the past decade, the use of DTI has proliferated, with scientists using it to gain insights into a host of neurological and psychiatric disorders, from epilepsy and addiction to head trauma. Additionally, it has been used to more precisely map the location of brain tumors prior to surgery.

Research indicates that white matter is composed of fibers connecting neurons from gray matter to other brain regions. According to Huang, this DTI technique shows structural changes within the fiber itself. The thinking is that some disease may be rooted in subtle "wiring" problems involving axons, the long, thin tails of neurons that carry electrical signals through the brain.

Their study involved 25 elderly subjects, some with mild Alzheimer's, some with normal brain function. Auchus and Huang wanted to see whether fractional anisotropy (FA), a measure of the directional diffusivity of water, might be different in the Alzheimer brain. They found that this change in white matter is associated with cognitive dysfunction in Alzheimer's disease. "DTI tracks the movement of water molecules in the brain. When water is not moving in a uniform manner, it means there is disease," said Auchus.

What their study found were changes present in the brain regions serving higher cortical functions, but not in regions serving primary function. "These different patterns of directional diffusivity change can be used to infer underlying pathologic mechanisms affecting various brain regions in a variety of neurologic processes," the authors wrote.

In their next study, Auchus and Huang, in collaboration with UTHSC movement disorder specialist Mark LeDoux, MD, PhD, want to use DTI to look at changes in white matter among subjects who have Huntington's disease. They are interested in this particular disease because, for people who have the gene, the onset of Huntington's takes place as the patient reaches middle age, usually during the 40s or 50s. Since Huntington's is a genetically linked disease, doctors know whether the abnormal gene is present with Huntington's even before neurologic symptoms develop.

"We want to look for some evidence of nerve cell changes as found in the Alzheimer's subjects. If we can make the same findings in the Huntington gene carriers, then we'll be happy and more confident that this can be used as a biomarker for brain degeneration," said Auchus.

Finding a reliable, valid biomarker would be a significant step forward in identifying those individuals who might be at risk for dementia and ultimately, provide treatment before the brain has been ravaged by disease.

"If this works, we don't have to wait until you're 75 when you're getting signs of dementia," says Auchus. "Instead, we can apply the biomarker in your 50s, and therefore detect the presence of disease earlier. Hopefully by then, we'll have treatment to stave off the onset of Alzheimer's and keep the brain from degenerating."

Huang added: "We want to detect the presence of changes in the brain before the patient shows signs. We want to achieve medications and treatments that will affect the process of the disease but also detect disease before it does much damage and intervene before it progresses. We want to stop the illness so it doesn't damage the brain to begin with."

While grant monies have been more difficult to obtain in recent years, Auchus said the tap to the federal pipeline has been loosened with the recent passage of Obama's stimulus package. He remains optimistic that he and fellow researchers at UT will be awarded the new funds they need to continue their work.

While the verdict is still out, Auchus said, "We keep following leads. We'll just have to see if there's a pot of gold at the end of the rainbow."

Tags:

Alzheimer's disease, DTI research, UTHSC

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