Non-invasive ultrasound restores memory in Alzheimer's mice

Ultrasound technology could provide a non-invasive way of treating Alzheimer's disease after researchers successfully restore memories to mice.

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Image by Garpenholm, CC BY-SA 3.0

A potential method of treating Alzheimer's disease using ultrasound is being hailed as a "breakthrough".

A team of researchers at the University of Queensland's Queensland Brain Institute Clem Jones Centre for Ageing Dementia Research have successfully restored memory function in mice using the drug-free, non-invasive technology to break down the neurotoxic amyloid plaques that cause memory loss and loss of cognitive function.

"We're extremely excited by this innovation of treating Alzheimer's without using drug therapeutics," said CJCADR director Professor Jürgen Götz.

"The word 'breakthrough' is often mis-used, but in this case I think this really does fundamentally change our understanding of how to treat this disease, and I foresee a great future for this approach."

To test the treatment, first the team deposited amyloid-β into the brains of the test mice -- the peptide that has been implicated with effecting Alzheimer's dementia. This creates a mouse model of the disease that can be used to test treatments.

These test mice were then treated with repeated scanning ultrasounds. The waves of these ultrasounds oscillate very rapidly, which activates the microglial cells that digest and remove the amyloid-β plaque that destroys synapses. When the brains of these mice were examined using spinning disc confocal microscopy and 3D reconstruction, the team found that these activated microglial cells had consumed a lot of the amyloid-β.

In fact, compared to the placebo mice, cleared plaques were observed in 75 percent of the ultrasound-treated mice. And these mice displayed much higher cognitive function -- they performed much better in three memory tasks -- the Y-maze test, the novel object recognition test and the active place avoidance test. In these tests, they performed at the same level as normal, healthy mice.

Although the human brain is different to the mouse brain, the team believes that, if applied early, the ultrasound approach could prove much more effective than Alzheimer's drugs, which are only effective for a short period of time and don't remove the Amyloid-β.

"With an ageing population placing an increasing burden on the health system, an important factor is cost, and other potential drug treatments using antibodies will be expensive," Professor Götz said.

"In contrast, this method uses relatively inexpensive ultrasound and microbubble technology which is non-invasive and appears highly effective. The approach is able to temporarily open the blood-brain barrier, activating mechanisms that clear toxic protein clumps and restoring memory functions. With our approach the blood-brain barrier's opening is only temporary for a few hours, so it quickly restores its protective role."

The next step is to further test the treatment to see if it can clear toxic protein aggregates in other neurodegenerative diseases, and whether, along with memory and cognitive function, it can also restore executive functions, such as decision-making and motor control. Human clinical trials are around two years away.

The full paper, "Scanning ultrasound removes amyloid-β and restores memory in an Alzheimer's disease mouse model", can be found online in the journal Science Translational Medicine.

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