Can ultrasound help remove amyloid?

The other day, I was driving home from the gym and saw my neighbor waiting at the bus stop in the cold.  Of course, I stopped to pick him up and take him to the library.  He's a retired physician who has macular degeneration and can no longer drive.  On the way, he mentioned that he'd seen a very interesting article in the New England Journal of Medicine (NEJM) about using ultrasound to speed the movement of Alzheimer's disease medications into the brain.  I had seen the news, although I hadn't looked into it very much.

Before and after this event, I actually heard from a couple of you who had seen the news stories and suggested I look into it.  Which I did.

Long story short, a team of researchers at the West Virginia University Rockefeller Neuroscience Institute used a device that could focus sound waves on different parts of the brain to improve uptake of Alzheimer's medication.  The sound waves briefly weakened the blood-brain barrier, allowing more Alzheimer's disease medication to get to the amyloid plaques than otherwise.  They hoped the medication would then be more successful at removing the plaques.

So how would this work?  We discussed the blood-brain barrier in Beating the Dementia Monster, but you should know that it has to do with the construction of circulatory system capillaries in the brain.  Capillaries throughout the body must run near cells so that oxygen and nutrients can escape the capillaries and get to the cells.  Carbon dioxide and cell waste molecules must also be able to enter the capillaries and be taken up by the blood for removal from the body.  So there are holes in the walls of the capillaries.

The brain has special needs unlike other parts of the body.  It has special needs for protection from microorganisms that cause infection, and so it is isolated from the rest of the body.  In fact, it has its own separate immune system.

The capillaries in the brain have smaller openings in the walls to allow nutrients and waste to pass between the brain and the blood.  This prevents larger molecules and particles, like bacteria and viruses, from entering the brain.  And monoclonal antibodies, like those in Aduhelm and Leqembi must pass through the barrier to get to the brain ... but they're kind of big.  So they need help.  And the ultrasound causes the openings in the capillary walls to open wider.

To do this, the researchers injected tiny micro-bubbles in the blood.  The sound waves cause the bubbles to expand and contract, and this causes the openings in the capillary walls to open wider.  

So how did the research on this work out?  According to this article (no, I didn't purchase the NEJM article), researchers have been working for years on techniques for using ultrasound to briefly weaken the blood-brain barrier.  And this turns out to have been a great opportunity to apply that research.

This was a "proof of concept" trial with only a few participants.  The researchers were pleased with the results, but we have yet to see if this will actually accelerate the removal of amyloid plaques. 

And then there's the other problem that we discussed before.  How effective are these monoclonal antibodies at improving the lives of Alzheimer's patients?  Does removing the plaques improve memory and cognition?  Is the "the amyloid hypothesis" valid?  This is not clear, but it's where most of the research money is going.  It will be interesting to see if future studies with ultrasound find that the technique actually produces improved memory and cognition.