Diagnostics

New brain imaging agent is marker for progression of Alzheimer’s

In the new study, the researchers used a compound that has a very high affinity for tau proteins.

Images across the top show compilations of PET brain scans of people who are cognitively normal. Images across the bottom show compilations of PET brain scans of patients with symptoms of mild Alzheimer’s disease. The difference between scans of healthy people and scans of patients with mild Alzheimer’s disease is much more apparent in the images that measure tau (right four images), suggesting tau protein buildup in the brain is a better marker of Alzheimer’s disease symptoms than the long-studied amyloid beta buildup (left four images).

Images across the top show compilations of PET brain scans of people who are cognitively normal. Images across the bottom show compilations of PET brain scans of patients with symptoms of mild Alzheimer’s disease. The difference between scans of healthy people and scans of patients with mild Alzheimer’s disease is much more apparent in the images that measure tau (right four images), suggesting tau protein buildup in the brain is a better marker of Alzheimer’s disease symptoms than the long-studied amyloid beta buildup (left four images).

A new imaging agent, called T807, that binds to tau protein and makes it visible in PET scans is showing promise as a marker for cognitive decline in Alzheimer’s patients.

This is according to a study, conducted by scientists at Washington University School of Medicine in St. Louis, published in the journal Science Translational Medicine.

Previous research has shown that elevated levels of a protein fragment called amyloid beta are the earliest markers of developing Alzheimer’s disease. Senior study author Dr. Beau M. Ances, associate professor of neurology at Wash U., said that many patients are cognitively normal in the earliest stages of Alzheimer’s disease, even with amyloid buildup.

Although spinal taps can detect amyloid and tau changes, this technique provides a picture of what’s occurring in the brain; it doesn’t tell the location of those changes.

“There are two new techniques. One is to look for amyloid in the brain using a scanning method that involves positron emission tomography, or PET. We make a compound that has a very high affinity for amyloid, and that is developed to bind amyloid in the brain,” said Ances.

The compound is injected into a patient’s arm, and after about 80 to 90 minutes, clinicians run a PET scan to see if there is increased uptake of the imaging agent in the brain. “If the brain lights up, if there is more binding in the brain, we are concerned, because they have an amyloid composition that is seeing those deposits in the brain,” said Ances.

In the new study, the researchers used a compound that has a very high affinity for tau. After injecting T807 into the patient and waiting a period of time, researchers also were able to see whether this protein binds.

“If it binds, that may not be a marker of Alzheimer’s, but it tells us something is abnormal occurring in these individuals,” said Ances. “We actually combined the two techniques,” said Ances.

The study involved a control group of 36 participants who were cognitively normal and 10 patients who had mild Alzheimer’s disease. “We saw this tau imaging technique was really important in that transition phase, when a person is going from cognitively normal thinking, from having no problems to starting to have mild changes,” Ances said.

When someone is starting to have thinking problems, the researchers can see the patient’s brain starting to light up with tau. Since amyloid changes early in the disease, those changes don’t really reflect as well when patients take traditional pen-and-paper tests, the study indicated.

“People can be chock full of amyloid in the brain and may not have a large amount of tau. By the time they develop amyloid and tau together, that is when things tip the person over,” Ances said.

The new technique is expensive and is not yet available to the public. “The dream is, you would have these kinds of measures out there, and people could be staged in the disease and we could evaluate therapies,” Ances said. “Drugs are starting to be developed that bind to the tau in the brain. We are now making better techniques in imaging and spinal taps to make a diagnosis.”

Dr. Jeff Burns, a neurologist at the University of Kansas Hospital, said, “This is an important first step in beginning to tease apart the underlying pathologies related to dementia. This is an early example of how the new era of molecular imaging will advance our understanding of this complicated disease.”

Photo: Washington University

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