Ultrasound Treatment for Amyloid in Alzheimer's Disease
Researchers are investigating the use of ultrasound to reduce levels of harmful amyloid in the brain. At this point it is showing benefits in mice, but there is a way to go yet before there can be any certainty that this strategy can also work in humans:
From imaging babies to blasting apart kidney stones, ultrasound has proved to be a versatile tool for physicians. Now, several research teams aim to unleash the technology on some of the most feared brain diseases. The blood-brain barrier, a tightly packed layer of cells that lines the brain's blood vessels, protects it from infections, toxins, and other threats but makes the organ frustratingly hard to treat. Safely and temporarily opening the blood-brain barrier is a long-sought goal in medicine. About a decade ago, researchers began exploring a strategy combining ultrasound and microbubbles. The premise is that ultrasound causes such bubbles to expand and contract, jostling the cells forming the blood-brain barrier and making it slightly leaky.Researchers hypothesized that the brief leakage would rev up the brain's inflammatory response against β amyloid - the toxic protein that clumps outside neurons in Alzheimer's and may be responsible for killing them. Disposing of such debris is normally the role of the microglia, a type of brain cell. But previous studies have shown that when β amyloid forms clumps in the brain, it seems to overwhelm microglia. Exposing the cells to antibodies that leak in when the blood-brain barrier is breached could spur them to wake up and do their jobs. Some antibodies in blood may also bind directly to the β-amyloid protein and flag the clumps for destruction.
Researchers recently tested the ultrasound strategy in a mouse model of Alzheimer's. After injecting these animals with a solution of microscopic bubbles, they scanned an ultrasound beam in a zigzag pattern across each animal's entire skull, rather than focusing on discrete areas as others have done. After six to eight weekly treatments, the team tested the rodents on three different memory tasks. Alzheimer's mice in the control group, which received microbubble injections but no stimulation, showed no improvement. Mice whose blood-brain barriers had been made permeable, in contrast, saw full restoration of memory in all three tasks. The team also found a two- to fivefold reduction in different types of β-amyloid plaques in the brain tissue of the treated group. The attempt to stoke microglia's appetite appeared to work; researchers found much more β-amyloid protein within the trash-eating cells of treated animals.