One promising possibility when it comes to treating Alzheimer's is the idea of using non-invasive ultrasound to take out toxic brain plaques, and a group of researchers in Australia have been at the cutting edge of this technology for a number of years. The scientists' latest investigations have uncovered some surprising new ways this technique can improve cognition in mouse models of the disease, which they believe could have wider implications for restoring cognition in the elderly.
Led by Professor Jürgen Götz at the University of Queensland, the researchers behind this promising ultrasound therapy published some exciting early results in 2015. Initially, the idea was to use ultrasound in combination with gas-filled microbubbles to temporarily open the blood-brain barrier to allow in drugs that take out toxic amyloid and tau brain plaques that destroy synapses and are seen as key drivers of Alzheimer's disease.
As it turned out, this technique proved an effective way to clear away the brain plaques without the need for any drugs, with the ultrasound activating microglial cells that could digest the plaques all on their own. The scientists then published a study in 2018 demonstrating how this technique could safely clear the toxic brain plaques and restore memory function in mouse models resembling human brains of 80 to 90 years old, and set their sights on human trials.
As they've continued to study this technique in mice, the scientists have continued to uncover new information about its effects on the brain, and how it might boost cognition. In newly published research, the team carried out new experiments on mouse models of brains with age-related deterioration, and found that it brought about yet further unexpected changes.
One of the physiological hallmarks of age-related cognitive decline is a deterioration in a type of signaling between neurons called long-term potentiation (LTP), which is associated with memory. The scientists were able to show that combining ultrasound with the microbubbles fully restored LTP in one region of the hippocampus. More interesting still, the ultrasound proved even more effective without the help of the microbubbles, not only restoring LTP but also improving the spatial learning deficits of the elderly mice by improving synaptic signaling and neurogenesis, among other physiological alterations.
These results indicate that the team's ultrasound technique could serve as a two-pronged attack on Alzheimer's, combining with microbubbles and plaque-busting agents to tackle the condition while simultaneously improving cognition via a separate pathway. And promisingly, the scientists believe the technique may one day prove a viable way to address age-related cognitive decline in the broader population.
“Historically, we have been using ultrasound together with small gas-filled bubbles to open the almost-impenetrable blood-brain barrier and get therapeutics from the bloodstream into the brain,” Professor Götz says. “The entire research team was surprised by the remarkable restoration in cognition. We conclude therapeutic ultrasound is a non-invasive way to enhance cognition in the elderly.”
The research was published in the journal Molecular Psychiatry.
Source: University of Queensland
