Diffusor tensor imaging: Moving water in the Alzheimer's brain

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  • Published: Aug 1, 2015
  • Author: David Bradley
  • Channels: MRI Spectroscopy
thumbnail image: Diffusor tensor imaging: Moving water in the Alzheimer's brain

Structure and biomarkers

Researchers at UK's Sanders-Brown Center on Aging are at the forefront of the search for biomarkers predicting Alzheimers Disease - Identifying Biomarkers Key to Early Intervention in Alzheimer's Disease (Credit: University of Kentucky Office of Public Relations)

Microstructural changes in the brain that occur in the fatal neurodegenerative disorder Alzheimer's disease have been detected using diffusion tensor imaging (DTI) magnetic resonance imaging (MRI), which can determine the diffusion of water in the brain. This coupled with reserach on protein biomarkers indicative of early pre-clinical changes in the brain could lead the way to a new early diagnostic for the disease.

Current evidence suggests that Alzheimer’s disease (AD) begins much earlier than any obvious clinical symptoms and so finding biomarkers for these deleterious changes might lead to a way to screen for the disease and perhaps offer treatment and counselling much sooner than is possible now. Mark Lovell of the University of Kentucky points out that autopsy is the only definitive diagnostic for AD, although positron emission tomography can identify the brain lesions that occur in this degenerative disease in living patients. An easy to spot, early-warning biomarker would be a much more useful diagnostic for doctors.

Avoiding the spinal tap

"Multiple studies show alterations in levels of the proteins associated with Alzheimer's disease - tau and beta amyloid - in cerebrospinal fluid, but a spinal tap to obtain that fluid is often a hard sell for patients," Lovell points out. Moreover, variability in these proteins makes it a temperamental diagnostic. Working with Bert Lynn, at the UK’s Mass Spectrometry Center, Lovell has been sorting spinal tap proteins by weight and identified transthyretin and prostaglandin-d-synthase as of potential interest. "We were able to tease out that these two proteins, when subjected to oxidative damage, tended to stick together and fractionate at a higher molecular weight than expected," he explains.

Further investigation points to these proteins being a sign of dysfunction in the brain's choroid plexus, which produces and filters cerebrospinal fluid. Changes in the transfer capacity of the choroid plexus have previously been associated with AD. Testing blood and urine samples was the next step. "I've been sceptical that blood can be as strong a predictor of Alzheimer's disease as cerebrospinal fluid, but I was pleasantly surprised to see that there was a reasonable correlation in samples of CSF and blood taken from the same patients," Lovell adds.

Functional image

A blood-based biomarker for AD that is more predictive than amyloid beta could be important. But, it might be that three or four biomarkers could be used in concert to obtain a definitive early diagnosis of the disease. As such, Lovell has worked with cognitive neuroscientist Brian Gold who is using brain imaging in his own AD research. "We’ve been focusing on microstructural brain changes detectable with a form of MRI called diffusion tensor imaging (DTI), which assesses the diffusion of water molecules in the brain," explains Gold. "As cellular structures begin to degenerate, tissue barriers degenerate as well, allowing for increased water diffusion DTI-based changes in the brain."

Gold's most recent findings using DTI and functional MRI correlate well with Lovell's CSF biomarkers, which could point the way to a minimally invasive way to diagnose pre-clinical AD.

Related Links

Neurol 2015, 70, 2212-2218: "An aberrant protein complex in CSF as a biomarker of Alzheimer disease"

Article by David Bradley

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

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