Ultrasound Therapy for Alzheimer’s

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.

Ultrasound may be a way to not just tackle brain plaques associated with Alzheimer’s, but also age-related cognitive decline in the broader population

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.”

Source: https://qbi.uq.edu.au/

A Cannabis Molecule Reduces Plaque, Improves Cognition in Alzheimer’s

A two-week course of high doses of CBD helps restore the function of two proteins key to reducing the accumulation of beta-amyloid plaque, a hallmark of Alzheimer’s disease, and improves cognition in an experimental model of early onset familial Alzheimer’s, investigators report. The proteins TREM2 and IL-33 are important to the ability of the brain’s immune cells to literally consume dead cells and other debris like the beta-amyloid plaque that piles up in patients’ brains, and levels of both are decreased in Alzheimer’s.

The investigators report for the first time that CBD normalizes levels and function, improving cognition as it also reduces levels of the immune protein IL-6, which is associated with the high inflammation levels found in Alzheimer’s, says Dr. Babak Baban, immunologist and associate dean for research in the Dental College of Georgia (DCG) and the study’s corresponding author. There is a dire need for novel therapies to improve outcomes for patients with this condition, which is considered one of the fastest-growing health threats in the United States, DCG and Medical College of Georgia (MCG) investigators write in the Journal of Alzheimer’s Disease.

Right now we have two classes of drugs to treat Alzheimer’s,” says Dr. John Morgan, neurologist and director of the Movement and Memory Disorder Programs in the MCG Department of Neurology. “One class increases levels of the neurotransmitter acetylcholine, which also are decreased in Alzheimer’s, and another works through the NMDA receptors involved in communication between neurons and important to memory. But we have nothing that gets to the pathophysiology of the disease,” says Morgan, a study coauthor.

The DCG and MCG investigators decided to look at CBD’s ability to address some of the key brain systems that go awry in Alzheimer’s.

They found CBD appears to normalize levels of IL-33, a protein whose highest expression in humans is normally in the brain, where it helps sound the alarm that there is an invader like the beta-amyloid accumulation. There is emerging evidence of its role as a regulatory protein as well, whose function of either turning up or down the immune response depends on the environment, Baban says. In Alzheimer’s, that includes turning down inflammation and trying to restore balance to the immune system, he says.

CBD also improved expression of triggering receptor expressed on myeloid cells 2, or TREM2, which is found on the cell surface where it combines with another protein to transmit signals that activate cells, including immune cells. In the brain, its expression is on the microglial cells, a special population of immune cells found only in the brain where they are key to eliminating invaders like a virus and irrevocably damaged neurons.

Source: https://jagwire.augusta.edu/