Scientists have successfully used ultrasound waves to break up the amyloid plaques in the brains of mice with a form of Alzheimer’s disease, in a study conducted by researchers from the University of Queensland in Australia and published in the journal Science Translational Medicine.
The intervention also improved cognitive symptoms in the treated mice.
The researchers hope that the findings could eventually lead to an inexpensive treatment for human Alzheimer’s disease, but many other scientists have expressed skepticism.
Alzheimer’s disease, the most common form of dementia, is an incurable, progressive brain disease characterized by loss in memory and the ability to perform daily tasks. It now affects more than 5 million people in the United States alone.
Dissolves plaques, boosts cognition
Ultrasound is already used as a therapeutic technique to help Alzheimer’s drugs and other brain-targeting drugs work better, because it causes breaches in the blood-brain barrier that protects the brain from foreign elements. In the new study, the researchers wondered if ultrasound, even in the absence of drugs, might provide a benefit to brains with Alzheimer’s.
“It was just exploratory. We thought we’d give it a go,” researcher Jurgen Gotz said.
Over the course of several weeks, the researchers performed ultrasound therapy several times on mice specially bred to develop amyloid plaques and an analog of Alzheimer’s disease. The therapy involved first injecting the mice with tiny gas bubbles, which increases the effectiveness of ultrasound. All mice were also given various cognitive tests, such as maze tests. The mice (along with a control group not treated with ultrasound) were then killed, and their brains were examined.
The researchers found that, in 75 percent of the mice, ultrasound led to a reduction in amyloid brain plaques (an average reduction of 56 percent). There was no reduction in the untreated mice. No brain tissue seemed to be damaged by the treatment. In addition, most of the treated mice performed better on cognitive tests right before their deaths than the untreated mice did.
The researchers believe that the ultrasound worked by opening the blood brain barrier and allowing a protein known as albumin to pass into the brain. This protein then boosts the activity of cells known as microglia, which clear out amyloids and other toxic proteins.
Others express skepticism
The researchers plan to test their method in sheep next and then, if all goes well, in human beings. However, many Alzheimer’s treatments that have shown promise in mice have ultimately failed to help humans with the disease. This is, in part, because human cognition is much more complex than mouse cognition. In addition, Alzheimer’s disease is more complex in humans, including components such as brain inflammation that are not present in mice.
This technique in particular may face extra hurdles in becoming a human treatment. The human skull is much thicker than that of mice, and is very hard to penetrate with ultrasound waves.
Neuroscientist Murali Doraiswamy of Duke University called the results interesting but wondered whether ultrasound would really provide a benefit over drugs that already exist to clear amyloid plaques from the brain.
“Depending on the [ultrasound] frequency you use, you can cause tissue damage,” he said.
“[I]t’s not obvious to me that ultrasound has a big advantage.”
It should be noted that Dr. Doraiswamy has served as an advisor for pharmaceutical companies that produce Alzheimer’s drugs that could be forced to compete with the ultrasound technique.
In human trials, drugs that remove amyloid plaques from the brain have mostly failed to actually alleviate the symptoms of Alzheimer’s disease.
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