Yo-El Ju

Great.

Thanks, Eric, for inviting me.

I'm super excited.

Well, I think there's two broad areas, at least that I'm aware of, in which sleep and neurodegeneration overlap.

One is with Alzheimer's disease and how sleep or circadian disruption may have a two-way direction with early Alzheimer's disease pathology, where we know, obviously, once people get Alzheimer's dementia, they have a very high prevalence of sleep problems.

But we now know that even in the preclinical stage, meaning prior to any cognitive symptoms, people may have sleep disturbances that are detectable through a variety of means.

Also, there's some evidence to suggest that having sleep disruption may promote or speed up

um, the, uh, the buildup of Alzheimer's disease-related proteins like amyloid plaques and tau tangles.

So, you know, in the past, say, 15, 20 years or so, there's been a lot of data, uh, you know, starting with mice in the Holtzman lab here at WashU that have really looked at the, uh, interaction between sleep and, um, Alzheimer's disease proteins.

Um,

And I think as time has passed and as the biomarker field in Alzheimer's disease has advanced, we're getting more and more of these data in humans as well.

So that's one large area that's, I think, of concern to many of us.

The other area in which sleep and neurodegeneration overlap a lot is in synucleinopathies, and this is a group of disorders that includes Parkinson's, dementia with Lewy bodies, multiple system atrophy.

We know that there's a specific sleep disorder called REM sleep behavior disorder that people who have that sleep disorder are at heightened risk of being diagnosed with one of those synucleinopathies within 5, 10 years.

So we know that sleep can be a signal and sometimes a very specific signal as to neurodegenerative disease processes that may be ongoing in the brain well before symptoms occur.

So I'm a sleep doctor by training.

So I think that non-REM sleep and REM sleep are both important.

They're like my children, right?

They are important.

But when it comes to at least amyloid and tau, we think that it is the slow-wave sleep, which is kind of the deep part of non-REM sleep, that's important.