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Could a blast of sonic waves restore memory lost to Alzheimer's disease?

A safe and well-understood diagnostic technology might treat a devastating brain disease -- Alzheimer's

Sonic waves, first used by submarines in World War II, might one day help those with Alzheimer's disease preserve or regain their ability to remember and navigate, a new study on mice suggests.

It's far from ready for use on humans, but the new research offers new possibilities for Alzheimer's therapy that involve neither drugs nor surgery. The study's authors said the same technique might help in treating other diseases that involve the abnormal buildup of proteins in the brain.

In mice bred to develop Alzheimer's disease, stimulating the forebrain with scanning ultrasound over six-to-seven weeks appeared to activate specialized immune cells in the brain -- called microglia -- to sweep up and dispose of excess amyloid, the new research found.

Compared with mice that did not get the ultrasound "treatments," those that did performed far better on a series of tests to assess spatial memory, long-term memory and short-term memory. In a maze designed to test a mouse's ability to navigate, treated mice whose cognitive function had become degraded by the accumulation of amyloid plaques in their brains reverted to normal levels of navigational skill.

The new research was published Wednesday in the journal Science Translational Medicine. Drug candidates aimed at altering Alzheimer's inexorable course have been disappointing. The study is the first to suggest that a safe, non-invasive and well-understood diagnostic technology might jump-start the brain's laggard trash-removal system and halt or reverse the disease's course.

"The potential for noninvasive treatment of Alzheimer's disease is exciting," said Dr. Michael Wolfe, an Alzheimer's researcher at Brigham & Women's  Hospital in Boston, who was not involved in the current study. Wolfe echoed the study's authors, however, in cautioning against premature hope.

To test whether sonic waves could prove useful in treatment, investigators repeatedly swept the energy of a scanning ultrasound beam across the entire forebrain of a mouse bred to develop the hallmark amyloid plaques of Alzheimer's disease. After six to seven weeks of such non-invasive "treatments," the cortical area taken up by the amyloid plaques was reduced 56% in those mice that got the treatment, and the average density of amyloid plaques in their brains was roughly halved.

Aside from the question of whether a treatment that works in mice would be as effective in humans, Wolfe said that the timing of such treatment in humans would be tricky. The brains of the mice studied had significant proliferation of amyloid plaques already, a condition that in many humans well precedes the appearance of dementia symptoms.

That means that if scanning ultrasound were to help humans, it "would need to be initiated long before a diagnosis of Alzheimer's disease" is being made now. That ultrasound would also need to come before the disease had killed a significant number of brain cells as well.

"The bottom line is that there is a long way to go before this noninvasive technique could be translated into a practical treatment for Alzheimer's," said Wolfe.

The authors of the study also found that scanning ultrasound -- which is widely used to peer into soft tissue -- might one day help to usher plaque-busting drugs into the brain. In mice, the sonic beam had the effect of temporarily opening the fine sieve that keeps most toxins circulating in the blood from entering the brain.

That so-called "blood-brain barrier" is crucial in protecting the brain from everyday threats, but it also makes the task of delivering drugs to the brain difficult.

Researchers demonstrated that sonic waves prompted the glial cells in the mouse brains to clear the accumulation of amyloid. But they acknowledged it was "equally possible" that the blood-brain barrier's transient opening, induced by the sound waves, somehow acted to reduce deposition of new amyloid plaques.

Wolfe noted that a technique that opens the blood-brain barrier -- and that probably would need to be applied repeatedly -- comes with dangers of its own. Though the study's authors call the use of sonic waves "noninvasive," Wolfe said it is "still disruptive" because the brain's natural barrier of defense is repeatedly disabled.

James Hendrix, director of the Alzheimer's Assn.'s Global Sciences Initiative, warned Alzheimer's disease patients and their caregivers that they should not, at this time, ask their doctors about scanning ultrasound as a treatment.

"We are still far away from knowing if this has potential as a therapy for people with the disease," said Hendrix.

"The effectiveness, safety and cost of using this treatment on people with Alzheimer’s are important questions in moving this research forward," Hendrix said. "This new data will help scientists determine the likelihood and viability of moving forward with additional testing."

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