January 13, 2015
Using a modified 3-D brain scan technique called magnetic resonance imaging, or MRI, researchers are moving closer to detecting Alzheimer’s at its earliest stages. Early detection could be critical for monitoring the effectiveness of new therapies and detecting problems at the earliest stages.
The technique combines MRI with an antibody that targets the toxic beta-amyloid that builds up in the brains of those with Alzheimer’s. The study looked at mice that had been bred to develop an Alzheimer’s-like illness. In these mice, the beta-amyloid appeared as dark areas on a brain scan at the very earliest stages of disease. Mice that were not prone to developing Alzheimer’s showed no dark areas.
The researchers also studied the brains of those who had died of Alzheimer’s. Dark spots appeared in these brains, but not in those who had died without showing signs of dementia.
Developed by researchers at Northwestern University, the noninvasive technique requires no surgery and could detect abnormalities years before symptoms develop. The findings appeared in the journal Nature Nanotechnology.
“We have a new brain imaging method that can detect the toxin that leads to Alzheimer’s disease,” said study author William L. Klein, a professor of neurobiology at Northwestern’s Weinberg College of Arts and Science. “Using MRI, we can see the toxins attached to neurons in the brain.”
Early diagnosis can be important, since the brain changes that cause Alzheimer’s can begin to take their toll a decade or more before the disease is suspected, and current experimental treatments may be most effective at this early stage. Early diagnosis also allows more time for patients to consider entering clinical trials and gives families better opportunities to plan for the future.
Previous studies using MRI and other brain scanning methods have revealed that in people with Alzheimer’s, changes to the brain occur years before the onset of symptoms. MRI studies have confirmed, for example, that areas of the brain affected by Alzheimer’s may start shrinking a decade before the disease is diagnosed. Various techniques have also been developed to detect the beta-amyloid deposits, or brain plaques, that are a hallmark of the disease.
This new MRI probe technology is detecting something different. It detects toxic beta-amyloid molecules, or oligomers, which may be present years before they clump together to form the plaques that current probes target.
“Noninvasive imaging by MRI of beta-amyloid oligomers is a giant step forward towards diagnosis of this debilitating disease in its earliest form,” said study author Vinayak P. Dravid, in the McCormick School of Engineering and Applied Science at Northwestern. “This MRI method could be used to determine how well a new drug is working. If a drug is effective, you would expect the amyloid beta signal to go down.”
The researchers also observed that in mice, the behavior of animals with Alzheimer’s improved after receiving even a single dose of the MRI probe. “While preliminary, the data suggests the probe could be used not only as a diagnostic tool but also as a therapeutic,” said study author Kirsten L. Viola. A molecule that detects beta-amyloid oligomers, such as the one used as a probe for MRI, has the potential to reduce the toxic effects of oligomers.
Further studies will be needed to determine the effectiveness of this technique in people. As other research shows, some people have significant accumulations of beta-amyloid in the brain but never progress to the memory loss and thinking problems of Alzheimer’s. These people may have an especially rich network of brain cell connections, or cognitive reserve, that protects against dementia onset. If certain parts of the brain are damaged by plaque buildup, enough connections may remain to leave memory and thinking skills intact.
It will likely be years before such scans become routinely available in most doctors’ offices. The findings, however, underline the progress that continues to be made in diagnosing Alzheimer’s at its earliest stages as investigators work to better understand the disease and find a cure.
Source: Northwestern University. Kirsten L. Viola, James Sbarboro, Ruchi Sureka, et al: “Towards non-invasive diagnostic imaging of early-stage Alzheimer’s disease.” Nature Nanotechnology. Dec. 22, 2014.