Jonathan Kipnis, neuroscientist: "What if we could clean our brains during the day without having to sleep?"

Jonathan Kipnis , a researcher at the University of Washington, studies how the immune system and the brain interact to understand neurological diseases and aging . In 2015, he discovered new blood vessels in our brains, a study published in the journal Nature that revealed a previously unknown direct connection between the brain and the immune system. Kipnis gave a lecture at the National Center for Cardiovascular Research (CNIC).

—How did your discovery change our understanding of neurological diseases?

—Most of what we know comes from studies in mice with diseases like Alzheimer's and Parkinson's, where disrupting the brain's lymphatic vessels worsens symptoms, suggesting their key role in removing waste. There's been a lot of talk about recent work in China. Apparently, some centers there are performing a procedure called lymphatic venous anastomosis (LVA) in Alzheimer's patients. It involves surgically connecting lymphatic vessels to veins in the neck to remove waste from the brain (or unclog blocked lymphatics). They claim to have seen marked improvements in these patients.

—Do you think it could be a future cure for Alzheimer's?

—It may be too soon to talk about a cure, but the possibility is intriguing. In fact, it reminds me of something that happened years ago, shortly after we discovered lymphatic vessels in the brain. I was at the University of Virginia and showed our findings to John Jane, a legendary neurosurgeon. He said, “This could play an important role in Alzheimer’s. Maybe one day we’ll treat it with neurosurgery.” At the time, it seemed like a crazy idea—about 10 years ago. But he was clearly more visionary than I was.

—So it's no longer a crazy option.

—I don't know if it can be cured, but I think improving and maintaining the function of the brain's lymphatic vessels could delay the onset of Alzheimer's. Curing an ongoing neurodegenerative disease is very difficult, but delaying its onset is a more achievable goal. Perhaps surgical approaches like AVL could help, but I don't think surgery is the universal solution. I think boosting lymphatic function with drugs or other noninvasive methods is more promising.

—What is brainwashing?

—The brain, although lacking lymphatic vessels, eliminates waste through a unique system in which cerebrospinal fluid (CSF) circulates through the brain and drains into the lymphatic vessels in the dura mater. This brainwashing process occurs during deep sleep and is key to preventing Alzheimer's, as the accumulation of waste can contribute to its development. Therefore, good sleep is essential for brain health.

—Are there other ways to clean the brain vessels?

—Yes, and the best one we know right now is sleep, especially deep sleep. During that phase, our brain seems to have the greatest cleaning activity. But waste removal in the brain is a two-step process. First, CSF must move through the brain tissue to collect waste. Then, it must be properly eliminated. Think of the brain as a house: you can put clean water in, but if you don't get the dirty water out, what's left is a swamp. It's important to produce new, clean CSF; remove old, dirty CSF; ensure good flow through brain tissue; and, of course, functional lymphatic drainage is critical. That's why I don't think one drug will solve everything; rather, a multifaceted approach will be necessary.

—As people age, they tend to sleep less and worse.

—If the brain really cleans itself better at night, we should explore ways to improve that process. Just as we help the immune system with vaccines, we could find ways to optimize brain cleansing. Imagine if we could develop a method so that instead of needing 7-8 hours of sleep, you could get the same benefit in just 2 or 3 hours. Or even more radical: what if we could cleanse the brain during the day, to eliminate the need for sleep? That's my dream, as crazy as it sounds.

—It seems like science fiction.

—Curing cancer was also a challenge just 20 years ago.

—Can the immune system remove waste from the brain?

—The immune system is like the maintenance crew in Formula 1. Even with the best driver (his brain), if the maintenance crew isn't working, he'll never win the race. If the immune system malfunctions, the brain also suffers.

—Is the immune system the next frontier for treating neurological disorders?

—Yes, 100%. For a long time, neuroimmunology lived in a dark age where the brain and the immune system were considered enemies. Now we know that they communicate, and that when well-balanced, the immune system can help the brain heal and function better. But of course, if it's overactive or dysfunctional, as in autoimmune diseases, then it can cause damage. That's why knowing how to modulate immune activity in the brain is critical.