Neurologist: The Real Cause of Brain Disease — and How to Protect Yourself | Dr. David Perlmutter

**Jesse Chappus** (0:00)
Coming up on today's show.

**David Perlmutter** (0:02)
These are the cells called the microglial cells that are taking the front of the stage now, because when they go south, it sets the stage for every type of brain degenerative condition that you could think of. When our blood sugar is elevated, when we become insulin resistant, when there are higher levels of inflammation in the body, these polarize our microglia away from being brain defending, away from being supportive to their threatening M1 configuration. What we're offering are the keys to the kingdom. Get your metabolic house in order and you will be going a long way to preserving brain function. It's that simple. The Lancet back in 2024 listed 14 lifestyle factors if they could be brought under control. The rates of dementia in the Western world would decline by 50%.
What's happening, however, is the rates of dementia are exploding, expected to triple by the year 2050 Not because we are aging, not because there's been a genetic change, so it's something environmental, like our food and our lifestyles, that are threatening the brain. You're wondering what is it. Is it food? Is it exercise? Is it sleep? Is it socialization? The number one thing that you can do to set yourself up for brain health is to...

**Jesse Chappus** (1:20)
Dr. Perlmutter, what are microglia and why haven't they gotten the respect they deserve?

**David Perlmutter** (1:26)
Microglia, and that's a very important name for people to remember, are the components of what's called the brain's innate immune system.
And what that means is really quite interesting because the whole notion that the brain had its own immune system is a very new idea. It was thought for years that, well, if there's an infection or something in the brain, that immune cells would come from the rest of the body, work their way through the blood-brain barrier and deal with the infection. And to some degree, that's true. But we now recognize that these microglial cells live there and they represent immunity in the brain. They've been seen for years and years and they were thought, when you looked at them just on a slide under the microscope, you'd see these cells connecting neurons and you thought, well, they're the glue. And that's where the term glia comes from. Microglia means glue. And it was thought that these were just structural components holding the brain neurons together. But the reality is, they're always moving around looking for things, looking for something to tidy up. So they are the immune system of the brain. But they do a lot more than that. And that's really what's so exciting is, you know, beyond just being on guard for infection, they're actually, when they are happy, and that's really, I think, the central part of what you and I are going to talk about today.
What we call M2, they're doing much more than just dealing with infection or waiting for something to happen. They're nurturing the brain cells. They're keeping the blood brain barrier intact, and they're actually fostering the formation and stability of synapses, which is where one brain cell connects to another, which is really fundamental as it relates to learning. So these are the cells called the microglial cells that are taking the front of the stage now. You know, they're in the spotlight because when they go south, when they become dysfunctional, it sets the stage for every type of brain degenerative condition that you could think of.

**Jesse Chappus** (3:28)
Okay, well, let's talk about the two different phenotypes, M2, M1.
Best we can, we want them in the M2 state. Let's talk about why they would switch and what inputs cause that.

**David Perlmutter** (3:42)
Very good question. And this shift in the brains of mucils away from being friend to being foe, shifting from M2 supportive to being M1 destructive, to be fair, that's a construct that scientists, neuroscientists have created for simply understanding this shift. There are a multitude of different phenotypes between M2 and M1. In other words, it goes through a lot of different, iterations until it's fully, a full on M1 destructive. But unfortunately, one of the main issues that forces our supportive M2 microglia to becoming M1 is age. And people would say, well, you can't do anything about that. You can't reduce the number of birthdays that you have. But here's where the story gets really interesting.
Because it's not our chronological age, in other words, the number of times that we've gone around the sun, it's our biological age. It's the marker of how youthful or aged our bodies are. And we can now test that with some very interesting blood work called methylation clocks.