New article: A lymphatic waste-disposal system implicated in Alzheimer’s disease

[Fiver]

NEWS AND VIEWS 25 July 2018
A lymphatic waste-disposal system implicated in Alzheimer’s disease
The discovery that a set of lymphatic vessels interacts with blood vessels to remove toxic waste products from the brain has implications for cognition, ageing and disorders such as Alzheimer’s disease.

The summary: https://www.nature.com/articles/d41586-018-05763-0
The article: https://www.nature.com/articles/s41586-018-0368-8

How does one maintain a healthy disposal system?

[Julie G]

Hi Fiver! We discussed this in detail when the discovery was first made several years ago.

From previous papers, sleep is the most important strategy to activate the "disposal" system. Even the loss of one's night's sleep resulted in significant accumulation of beta-amyloid. One paper found that side sleeping (mouse model) allowed for more efficient clearance. Another paper found that very light drinking of alcohol cleared abeta better than no alcohol or heavy drinking. Dr. Ram Rao, a neuroscientist, who's worked in Dr. Bredesen's lab also recommended mild inversion yoga poses, like downward dog to activate. Others have spoken about lymphatic massage.

What are you finding?

[Fiver]

Hi Julie! I remember when they "re"discovered the brain's lymphatic system. Fascinating what old discoveries get ignored until they end up being important a century later! Nice to see the new progress, and attention (like this article and summary in Nature).

For me the most interesting thing is that there seem to be two separate lymphatic pathways, each with their own tendencies to work and/or fail over time. I'm fascinated by the path the AB can take along the outside of brain blood vessels because it seem clear that this would be "powered" by pulse waves of the arteries....with help from a good downward dog pose maybe! exercise or jumping up and down on a rebounder. Or other things. It also seems that anything that squeezes this space closed - maybe inflammation, swelling, hardening, high blood pressure, or cerebral coronary amyloiosis (clogging of the vessel lining) - would inhibit AB clearance.

It is making sense to me. And seems consistent with other observations about the timing of AB accumulation, infections in the brain, E4 parts aggregating with AB parts, etc. If AB antibodies don't work and if AB is really important to fight pathogens or grow brain regions (ala recent Tanzi et al. work)....this makes all that ok, as one could just ensure good clearance and prevent accumulation.

It also has a nice "physical" aspect I can wrap my brain around....in other words, it's kind of just a plumbing problem, right?

There are a lot of approaches to fixing plumbing. Widen the pipes. Increase the pressure gradient. reduce the viscosity of the fluid. Push backwards to clear a clog. And everything flows better.

I still have some basic questions that make me feel dumb. Like if sleep promotes really good lymphatic clearance why not sleep A LOT or use drugs to open up the lymphatic system in patients with high AB loads? If we can see AB levels go UP with one night of no sleep can we see it go DOWN with a good, long night's sleep? I can't find any data about that. Why not take an NSAID before bed to open up the lymphatic system more? Why not reduce outside pressure - sleep at altitude, maybe? Or use gentle sound waves to massage open the pathway?

If we had access to a PET scanner....we can just try these things and see right away if AB levels went up or, more to the point, down in response. Without that, how could folks know if their "waste disposal system" was working?

The more I read the less I feel I understand it. Smarter people must know these answers.

[Julie G]

Smarter people must know these answers.

I doubt it, Fiver. You're smart, passionate, and asking the right questions. Do you ever correspond with study authors to ask these important questions?

[Fiver]

Sometimes. I'll send a note. Or a tweet. If it a really beautiful study - great data, stats, figures, and writing it's like a piece of art (for this geek, anyway ) and it's just nice to let them know the hard work is appreciated. Most study authors reply right away and are happy to answer a few questions, which is great! Some are running really large operations and don't have time, understandably.

[Jafa]

Received this in my email inbox, an interview with Dr Tanzi, in which amongst other things he references the importance of 8hrs sleep (my seemingly unattainable Everest).


https://www.beingpatient.com/alzheimers-prevention-2/

Dr. Tanzi: I was thinking about an easy way to describe how you can shield your brain from Alzheimer’s. The six parts of SHIELD are the following:

Sleep

It’s never been more important to get eight hours of sleep. You don’t have to get eight hours of consistent sleep. You want to go into a dream cycle like REM, but when you come out, you’ll go into the deepest sleep—slow-wave sleep. That’s when the ‘scrubbing bubbles’ (the microglia, or the janitors of our brain) hit; they eat up debris in the brain. Some of the debris get forced out of the brain into the spinal fluid. I like to call this kind of sleep ‘mental floss,’ because that’s when you clean your brain. You have to allow yourself to sleep enough during the day and to go in and out of enough dream cycles so that you go into this rinse cycle several times. If you only slept for five or six hours, take an hour-long nap and a second hour-long nap. If you don’t get eight hours of sleep, you will accumulate more debris that will cause more inflammation in the brain.

Interesting take on the REM/non-REM transition - my understanding was that glymphatic clearance was a deep sleep activity, but it seems that REM sleep is perhaps an activator. What then of the effect of medications which inhibit REM sleep - hypnotics including the Z drugs, SSRIs. Thoughts?

[ChipW]

Interesting take on the REM/non-REM transition - my understanding was that glymphatic clearance was a deep sleep activity, but it seems that REM sleep is perhaps an activator. What then of the effect of medications which inhibit REM sleep - hypnotics including the Z drugs, SSRIs. Thoughts?

this paper seems to indicate that drugged sleep is as good as regular sleep. As someone who has trouble staying asleep more than 4 hours, this is interesting to me. any thoughts on this?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4636982/

"This analysis of CSF influx showed a striking similarity between true sleep and anesthetized mice. The sleep-wake difference in glymphatic influx correlated with the volume fraction of interstitial space that was 13-15% in the awake state an expanded to 22-24% in both sleep and anesthetized mic"

[circular]

Dr. Tanzi: I was thinking about an easy way to describe how you can shield your brain from Alzheimer’s. The six parts of SHIELD are the following:

Sleep

It’s never been more important to get eight hours of sleep. You don’t have to get eight hours of consistent sleep. You want to go into a dream cycle like REM, but when you come out, you’ll go into the deepest sleep—slow-wave sleep. That’s when the ‘scrubbing bubbles’ (the microglia, or the janitors of our brain) hit; they eat up debris in the brain. Some of the debris get forced out of the brain into the spinal fluid. I like to call this kind of sleep ‘mental floss,’ because that’s when you clean your brain. You have to allow yourself to sleep enough during the day and to go in and out of enough dream cycles so that you go into this rinse cycle several times. If you only slept for five or six hours, take an hour-long nap and a second hour-long nap. If you don’t get eight hours of sleep, you will accumulate more debris that will cause more inflammation in the brain.

Interesting take on the REM/non-REM transition - my understanding was that glymphatic clearance was a deep sleep activity, but it seems that REM sleep is perhaps an activator. What then of the effect of medications which inhibit REM sleep - hypnotics including the Z drugs, SSRIs. Thoughts?

I'm not sure if REM is an activator or just, according to Tanzi, the prior sleep cycle to the slow wave deep sleep. I suppose that's just a semantic difference.

Lately I've been using my Fitbit again. They say something different: '[Your body] usually moves from light sleep to deep sleep, back to light, then into REM, though sleep cycles vary naturally'. I wonder how Dr. Tanzi and the Fitbit team can be saying different things?

The Fitbit software has improved since I last used it. You might like getting to know the parts of your night's sleep that are going well, to balance out the frustration of not getting eight hours yet. Lately I added Skullcap and Life Extension Circadian Sleep with melatonin and nobiletin from citrus peel (warning that last ingredient is only based on mouse studies!). Instead of getting eight hours on my good nights I get seven, but I feel better. For the last week my deep sleep, light sleep and REM were all either within or above the typical range for women my age (percentage of sleep rather than total amount), while I've been awake less than the typical range My deep sleep cycles are mostly before any REM but with some exceptions, consistent with what Fitbit says is the norm.

I'm not sure being compared with women my age is ideal! And mind you this data isn't all that a formal sleep study is, but I think it may be useful for trends over time.

[donbob]

Our yoga class always does an inversion at least once. She occasionally mentions “this pose is an inversion because your head is below your body”. I wonder if it has to do with the lymphatic system? I’ll try to remember to ask.

[circular]

Our yoga class always does an inversion at least once. She occasionally mentions “this pose is an inversion because your head is below your body”. I wonder if it has to do with the lymphatic system? I’ll try to remember to ask.

It's also about blood flow to the brain, and I always thought it was interesting that Muslims invert their head in prayer fives times a day.