Alzheimer’s disease, the most common form of dementia, is characterized by the buildup of toxic, sticky plaques inside the brain. These plaques are made of a protein called amyloid-beta. Although hundreds of drug candidates that try to remove amyloid-beta from the brain have been tested in clinical trials, these have been a resounding failure (see “Where’s our cure to Alzheimer’s disease?”). This has led scientists to try out new methods for treating the disease.
One of the most intriguing ideas for treating Alzheimer’s is to use ultrasound. Ultrasound uses high-frequency sound waves outside the range of human hearing. These sound waves can pass through soft tissues but bounce off of denser things such as bone, which is how ultrasound can generate the image of a fetus during pregnancy.
Ultrasound has many uses outside of imaging. One recent techniques involves injecting the patient with tiny “microbubbles.” When hit with an ultrasound pulse, the microbubbles expand and contract. This allows them to gently press against the blood vessel walls without damaging them.
The microbubble ultrasound technique has an interesting effect inside the blood-brain barrier (BBB). The BBB is a complex structure that surrounds blood vessels inside the brain. It prevents harmful toxins and pathogens from entering the brain, but can also make it difficult for waste products (including amyloid-beta) to be cleared away.
The cells surrounding blood vessels in the brain, known as the blood-brain barrier, prevent large molecules from passing through. Image Source
When microbubbles inside the brain’s blood vessels expand, they can temporarily open the BBB. This not only allows for enhanced clearance of waste products, but also activates many immune pathway in the brain that further assist with this process.
Early experiments involving mice have been encouraging. In 2013, 2014, and 2015, three different research groups found that mice that were genetically engineered to develop Alzheimer’s disease showed improvements after ultrasound/microbubble treatments. This included reduced levels of amyloid-beta, improved spatial memory, and more newborn neurons inside the hippocampus, a part of the brain associated with memory.
Several human trials involving ultrasound are currently being planned or in progress. One small trial of five subjects found that the ultrasound device could safely and reversibly open the BBB. However, we still need to wait for more results to come out before we’ll know whether this strategy is effective for treating Alzheimer’s.
It also remains to be seen whether ultrasound may come with any unforeseen consequences. It’s possible that opening the BBB could allow certain immune cells or pathogens to enter the brain, creating an opportunity for autoimmune reactions or brain infections. Despite the potential risks, researchers remain hopeful that ultrasound could offer a noninvasive means for treating Alzheimer’s disease in the future.
AlzScience 