Missing link between Alzheimer’s and vascular disease found? | Hacker News Reader

Missing link between Alzheimer’s and vascular disease found?

cuimc.columbia.edu

138 pointsgeox56 comments

The link through a gene is interesting, but that may not be the only link.

We work in the sleep space at https://soundmind.co, specifically working on increasing the effectiveness of deep sleep through stimulating slow-wave oscillations.

Current research in the stimulation we are using is looking at the impact of stimulating SWOs on diabetes, as well as the impact on clearing of amyloid plaques.

There is also a relationship between cortisol and hypertension, cortisol is also improved through proper sleep, and the stimulation we are working with.

I'm not saying altering genes is not the solution, but how many people have the FML2 gene, and this research was on zebrafish and mice. The research we are have implemented is in people.

Are you recommending people use a non-approved medical treatment?

Relax, it's a head band that plays sounds. Not some weird peptide cooked up in a lab.

sure it's not harmful directly, but indirectly if you're treating yourself with a headband that plays sounds you might neglect to get actual treatment.

Actually, you'd be surprised. This is neuroscience. It is possible to collapse the SWO wave. Do this enough in one night and you'll feel like you've got a hang-over the next day.

But if that were to be happening, we'd recognize in the headband that the wave is collapsing and either we are not stimming properly, or the person is having a negative response to the stim. Either way, we'd stop the stim to prevent damage.

Absolutely not.

I'm stating that research is currently underway to discover if this is an effective prevention to amyloid build up resulting in Alzheimers.

how does soundmind compare to the dreem headband?

It's the same science.

1. We're more specific in market we are targeting (we'll be more specific as we get closer to launch based on early cohort analysis).

2. Subscription rather than big up front fee

3. Better more comfortable headband design. It's unique, but not "weird". Strangely light and cool (both temperature and style).

I'll admit I'm biased, but I believe Dreem should have been a much bigger success than it was.

I see from your comments you have a deep interest in sleep. Feel free to ping me on linkedin - details in profile.

> cerebrovascular disease, by interacting with FMNL2, reduces the clearance of amyloid in the brain.

Hopefully, this sets the stage for a targeted therapy which could finally test the amyloid beta theory:

"When drugs that have been shown to reduce amyloid-β are given to people who are expected to develop Alzheimer’s disease and they still don’t work, says Murphy, “that would absolutely convince me we’ve been misled and it has to be wrong”."

(From https://www.nature.com/articles/d41586-018-05719-4 )

We have drugs that remove amyloid-B, they didn't have any effect in clinical trials. (Despite one passing FDA approval)

The problem is it was given to people who already had Alzheimer's. And I doubt they'll ever get permission from an IRB to run the study on a patient who are just expected to maybe develop Alzheimer's.

I think it's more of an amyloid-B as scar tissue thing. Whats causing the insult to create scar tissue in the first place, and if the body didn't make amyloid-B, what worse thing would happen?

The disease may have multiple causes. I wouldn't at all be surprised if some other area of health decline gives rise to the disease state. A number of investigators are looking into vascular health, for instance.

Here's an article I posted a while back that implicates liver health and was able to mechanistically induce the disease in rat models:

https://news.ycombinator.com/item?id=29393937

The same team is now launching a phase II study to test Probucol:

https://pubmed.ncbi.nlm.nih.gov/35190446/

"recent studies suggest that increased plasma concentrations of lipoprotein-Aβ compromise the brain microvasculature, resulting in extravasation and retention of the lipoprotein-Aβ moiety. The latter results in an inflammatory response and neurodegeneration ensues. Probucol, a historic cholesterol-lowering drug, has been shown in murine models to suppress lipoprotein-Aβ secretion, concomitant with maintaining blood-brain-barrier function, suppressing neurovascular inflammation and supporting cognitive function."

The book "The End of Alzheimer's" by Bredesen postulates that there are around 36 risk factors for Alzheimer's. It takes many of them in combination to cause the disease.

This is why studies isolating just one factor have failed to find a significant correlation. It's why there will likely never be a pill to cure it.

The book suggests therapy addressing all of the risk factors. Most of those are simply healthy living. Personally, I've been bending my lifestyle to conform to those. Can't hurt.

I recommend to take a look at this interview by the very Bredesen, to a scientist called Dayan Goodenowe, working also on the Alzheimer problem. He has a very interesting book called "Breaking Alzheimer" that postulates that DHA Plasmalogen deficiency is causative for Alzheimer. Very interesting stuff:

https://www.apollohealthco.com/facebook-live-plasmalogens-an...

Thanks for the link! Frankly, it sounds too good to be true. But I'm not qualified to judge this.

I agree Dr. Bredesen's protocol probably can't hurt as it advocates a healthy lifestyle and diet, but there is NO evidence that it can prevent or reverse Alzheimers[1], as he claims. Also, Dr. Bredesen charges $1800+ for the protocol[2] in addition to selling branded supplements.

1 - https://www.ucsf.edu/news/2020/05/417431/pricey-protocol-not... 2 - https://www.healthleadersmedia.com/clinical-care/alzheimers-...

There is evidence, but I agree it is not rigorous and does not rise to the level of proof. I hope it can inspire other researchers to research parts of it more thoroughly.

With respect to Dayan Goodenowe and his Plasmalogen theory, I think the Rush study should be reproduced by other groups. I am no qualified to judge it either, but thinking critically, unless some glaring statistical mistakes were made, or error measuring the levels, or simply that plasmalogen deficiency is a biomarker more than causative (he goes at length as to why he considers it to be the latter), we are talking about natural compounds (Plasmalogen precursors, or IV plasmalogens) that do not require FDA approval, so it should be fairly straightforward to fund, develop and test.

“The clinical implications of this study are obvious. This is the first reported evidence of a metabolic phenotype with the same clinical characteristics as the APOE ε2ε3 genotype. The probability of dementia in participants with either a high PBV or an APOE ε2ε3 genotype was indistinguishable”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6523320/

It's also worth noting that cerebrovascular disease can cause a dementia with symptoms just like alzheimers (without actually having alzheimers). It's literally called vascular dementia: https://en.m.wikipedia.org/wiki/Vascular_dementia.

If you're worried about forgetting your loved ones, do your best to control your vascular risk factors.

Vascular Vs degenerative (Alzheimer's) dementias are quite different in everything (symptoms, prognosis, therapy). Only the end stage of each is similar. And there is the mixed dementia which shares characteristics from both.

If you are looking for a mechanism for why a healthy vascular system protects against alzheimers there's a pretty good candidate here.

https://www.youtube.com/watch?v=He6HMnMbxAc#t=15m09s

My TL;DW is:

* Most neurodegenerative diseases are associated with a buildup of proteins.

* The brain does not have the lymphatic system which cleans waste proteins out of other organs.

* Instead it has cerebro-spinal fluid, which may have some of the same function.

* There's no "CSF-heart" that pumps CSF around the brain.

* Instead the pulse in the arteries has an indirect pumping effect because the arteries in the brain are embedded in CSF.

* Therefore having a healthy pulse/blood circulation serves to help clean the brain.

* But only when you sleep, so don't skimp on the sleep time HN-readers!

As a sleep-tech founder, I completely agree with the "don't skimp on sleep" part.

* The brain doesn't work on the lymphatic system, but on the glymphatic system [1] * The glymphatic clearance mostly occurs in slow wave sleep, and linked to slow oscillations (just happens to be the function of sleep we are focusing on at https://soundmind.co) [2]

1 - https://neuronline.sfn.org/scientific-research/understanding....

2- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698404/#:~:tex....

Seems logical then that people who develop alzheimers may have a dysfunction in this part of their sleep cycle no? Or could just be simple insomnia and years of lack of sleep

Current belief is both.

The reason you get Alzheimer's at a later stage in life is because as we age sleep degrades, a big part of this degradation is that we get less slow wave oscillations as we age. Less SWOs, means more build up of amyloids.

Years of lack of sleep also leads to build up of amyloids.

Of course this is only meaningful if the amyloid Alzheimer's connection is solved.

> * The brain does not have the lymphatic system which cleans waste proteins out of other organs.

The brain has a lymphatic system:

https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.120.31849...

Listening to matthew walker speaking on joe rogan, he said there was a huge correlation between getting little sleep and getting alzheimer's.

I also think having good circulation is important. I also remember reading that people who took viagra had lower chances of getting alzheimer's as well. viagra helps with circulation.

(so, sleep well and exercise)

I also find it amusing the article doesn't point to lifestyle changes as a possible answer, but to a possible drug solution :)

I thought most of the claims of that book had been debunked.

I don't know... but there are some articles here:

https://www.nih.gov/news-events/nih-research-matters/sleep-d...

https://www.nih.gov/news-events/nih-research-matters/viagra-...

Here's the debunking: https://guzey.com/books/why-we-sleep/

Viagra is also a direct neuroprotectant and phosphodiesterase(5 I think) is implicated as influencing intelligence through a GWAS.

Did someone try to remove amyloid plaque from the brain of an Alzheimer's patient and see what happens? I've heard of studies that disproved the amyloid theory.

There were at least 17 unsuccessful clinical trials (phase II and III) that tried to do that:

https://clinicaltrials.gov/ct2/results?cond=Alzheimer+Diseas...

As far as I can tell, no therapy has been successful in removing or preventing specifically either or both of beta and tau amyloid without secondary effects that washed out any prospective benefit.

The amyloid hypothesis is of course disputed, but largely because stopping whatever causes plaque formations could prevent or lessen the impact of Alzheimer's has proven so difficult and would ultimately provide little benefit to those already suffering with the disease.

The closest we've come to removing plaques, I should mention, is aducanumab, which does seem to reduce beta, but has little to no effect on even slowing cognitive decline, much less stopping or reversing it. Nonetheless, the FDA has approved this drug, paving the way for Biogen to charge $56K a year for the treatment.

https://n.neurology.org/content/98/15/619

No idea why you are being downvoted.

Yes, removing the plaque has been tried and has so far been unsuccessful at improving Alzheimer's.

The way I picture it (and I'm not an expert, still learning about this stuff myself) is to look at amyloid plaque as a clog in a pipe between nerve cells. Now picture the blockage putting a crack in the pipe. You can clear the blockage, but you still have a cracked pipe, so anything you send down the pipe will spill out.

We have no way of fixing the broken pipe, so we must prevent the build up of the plaque in the first place.

Checkout Annovis Bio, starting phase 3 soon I believe. They've had some success in Parkinson's disease.

I would also point to the effects of lipid peroxidation, of which it sounds like the “toxic proteins” at the root of the matter may be a product of. In any case, I’ve gone back to using normal deodorant.

Can you point me to anything to read on why you’d want to do that?

Aluminum, and other metals, aren't good to stuff into the holes in your skin.

Source: sense

Seconding your confidence in normal deoderant.

I can't stand perfumes and in the past I've had reactions to antiperspirants. So: Daily shower with soap and water. Ideally after any workout (so the closer to a blue collar day I've had the later the shower).

Migraines and or autoimmune issues?

The smell of a lot of laundry detergents makes me feel sick unless I go find the ones with no added scents. I assumed it was just an allergy at most.

Migraines can make sense of smell drastically stronger. A super power that really stinks.

I think a lot of people overuse deodorants and anti-perspirants. But now I wonder how many people don't shower every day and thus do really need to use them.

Nah. I shower at least once a day, sometimes two and still I will perspire as soon as I walk.

And I would even say that I sweat a lot less when I can’t shower, which could make sense given that taking a shower basically removes the oily film of the skin.

tbf, while I take a shower everyday because it feels good (and it’s what is socially acceptable), I really think we are not made to be washed frequently. I doubt our hunter-gatherers washed themselves everyday with soap. Yes we have better hygiene but still, I doubt our skin like it.

What kinds of deodorant aren't "normal"?

Ones without aluminum based ingredients - there was some science that indicated aluminum caused Alzheimer's but I think the evidence has shifted towards other things enough that they're fine. The alternatives were brands like Tom's that just didn't function like the real thing.

For what it’s worth in regards to good sleep, a good mattress goes a long way not expensive but one right for you. There’s many types.

Inflammation and inflammatory diet is linked to Alzheimer's: normally at night during sleep cycle the channels in the brain open up more to allow waste to exit the brain more easily, but if inflamed then the channels can't open up as much, and so arguably it can't as efficiently as it needs to clear out; repeat this every night over 40+ years.

I hate to invoke this but, Betteridge's law of headlines?[1]

[1]https://en.m.wikipedia.org/wiki/Betteridge%27s_law_of_headli...

Edit: somewhat tongue in cheek, because this does sound promising.

https://en.wikipedia.org/wiki/Betteridge%27s_law_of_headline...

The question mark always makes me extra suspect of the headline.

The general pattern holds, but to be fair, this one seems like it could best be answered with “Maybe”.

> "Maybe."

Aka "probably 'no' without further evidence."

I think the important observation of the "law" is that headlines are generally only phrased as a yes/no question when there isn't sufficient support for just stating them as a statement. "Can jellybeans cure cancer?" no, almost certainly not, or the headline would be "evidence jellybeans can cure cancer".

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