Alzheimer’s Treatments Could Go Acoustic

Ultrasound could offer a nonpharmaceutical method to treat Alzheimer’s disease, according to a new study.

Two scientists demonstrated that bombarding mouse brains with sound waves not only removed disease-related amyloid-β plaques but also restored memory in mice with Alzheimer’s-like symptoms.

In the clinic, doctors mostly use ultrasound to image patients’ tissues. But some researchers have started to use acoustic waves to improve drug delivery. For example, neuroscientists have developed ultrasound methods to temporarily open the blood-brain barrier, the cellular wall that controls what can move from the bloodstream into the brain and vice versa.

Jürgen Götz and Gerhard Leinenga of the University of Queensland, in Australia, thought that if others could soften the barrier to get cargo in, maybe they could open it to get unwanted substances out.

The Queensland scientists envisioned this ultrasound strategy removing amyloid-β plaques, the characteristic peptide deposits seen in the brains of Alzheimer’s patients. They tested their method on genetically engineered mice that spontaneously produce these brain plaques and exhibit memory deficits.

In the ultrasound experiments, the researchers first injected the mice with bubbles of a fluorinated gas encased in lipids. These 1- to 10-µm-wide bubbles helped transform sound waves applied by the team into mechanical energy that then loosened the tight junctions of the cells forming the blood-brain barrier.

After five treatments over six weeks, the brain area containing amyloid-β plaques was 56% smaller in treated mouse brains than in those of untreated animals. Also, the ultrasound-exposed mice outperformed unexposed ones in tests of the animals’ ability to remember familiar objects or visual cues (Sci. Transl. Med. 2015, DOI: 10.1126/scitranslmed.aaa2512).

Through further experiments, Götz and Leinenga determined that opening the blood-brain barrier cleared the plaques by activating microglia, a type of immune cell found in the brain. The researchers think that molecules from the bloodstream, such as albumin, move into the brain to activate the microglia, coaxing them to engulf and digest amyloid-β. There was no evidence that amyloid got cleared into the bloodstream, as Götz and Leinenga initially expected.

A team of researchers at the University of Toronto last year reported similar effects of ultrasound on another type of Alzheimer’s mouse (Radiology 2014, DOI: 10.1148/radiol.14140245). The new paper extends and verifies those earlier findings, says Kullervo Hynynen, one of the researchers involved in the 2014 study.

The concept of using ultrasound to clear out amyloid-β is definitely intriguing, says Terrence Town of the University of Southern California. His main concern is whether the method can work in people without causing damage. He points out that Alzheimer’s patients already have disrupted blood-brain barriers. “So if you’re going to go in and tickle the blood-brain barrier with ultrasonic bubbles, you will have to be very careful that you’re not going to make matters worse,” he says. “So I’d say proceed with caution.”