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- Hacker News
- This pertinent paper appeared more than a decade ago about the flaws in the amyloid plaque hypothesis: https://pmc.ncbi.nlm.nih.gov/articles/PMC4207354/
Many people without dementia show amyloid plaques in their brains in autopsies. It's becoming more accepted now that there are multiple interrelated causes after decades pursuing the simplistic amyloid plaque theory.
The article is bordering on irresponsible.
by djray - Anything that might fix brain plumbing would be welcome.
Over time, everything breaks down. If this actually fixes some plumbing issue that would be great. Of course, it probably will lead to another downstream plumbing issue, but one thing at a time.
by mannyv - Maybe a slight problem is liver toxicity at the doses in this study? The drug was tested at lower doses for other diseases, but above 72 mg caused problems. Quick conversion math is telling me this study would want 170+ mg.
Maybe there’s some way to get around this particular issue.
by janalsncm - I think it's immoral and unkind to report on a medical trial and not be clear that it was in mice rather than humans.by adaml_623
- In some parts of the world, it is recommended that drinking water be stored in copper containers. I'm wondering if these communities had figured something out about the health benefits of ingesting trace amounts of copper?by mlmonkey
- There's no need for missing answers as to why copper is appreciated as a water transport/storage medium. It's the same reason it's traditionally used as cladding on boat hulls, and is still added to many anti-fouling bottom paints - it's antimicrobial, but also toxic.by pengaru
- btw definitely related and seems significant:
they found people who use glucosamine (joint pain, knees etc)
have a 25% higher chance of Alzheimer's progression
https://thesciverse.org/scientists-found-that-a-supplement-t...
(still can't figure out if that website is "AI" but they have great articles)
by ck2 - note this is only the case for those with early-stage cognitive decline. for healthy individuals, it actually has neuroprotective effects.
> Glucosamine mimicked the effects of a low-carbohydrate diet in a prior animal research, resulting in increased lifespan [21], and studies consistently showed that a low-carbohydrate diet protects against dementia [22, 23]. An animal study suggested that glucosamine may promote cognitive function by impacting energy metabolism [20]; other animal models have indicated the neuroprotective and anti-neuroinflammatory effects of glucosamine
- Yep it's all AI-generated. It's annoying that they have a fake human as the author but whatever, it's the interslop.by plaguuuuuu
- My mother has early onset alzheimer's disease. We currently know very little about the disease and the current treatment options are controversial. The efficacy of the medications removing the amyloid plaque from the brain is questionable, as people still decline.
What makes alzheimer's difficult is that it is not really a single uniform disease. There are subtypes.
Since my mother has it, I was presented with an option of a genetic test. There are several genes which increase your risk. However, if one has PSEN1 that will 100% guarantee early onset alzheimer's at some point.
I'm still on the fence if I want to know.
I really hope we get some viable treatments for this terrible disease. Early onset azlheimer's is awful. I cannot imagine having malfunctioning brain.
by avgDev - It’s sometimes frustrating to try to explain that the gene mutation in the family (PSEN1 in our case) means it’s a 100% chance you get it. Most people have never heard of it, so you get a lot of “well, maybe you’ll be lucky and it won’t affect you!” from well meaning people.
I’m very sorry for what you’re going through with your mom. My father in law had it and died a year ago at age 64 after 16 years of decline. Watching a truly brilliant person slowly lose their faculties and abilities until they don’t recognize their own family is awful.
Two of his kids have the mutation (not my wife, thankfully) and so we all hope that better treatments are available for them.
by armadsen - Give her -- and yourself -- lithium orotate. It's an asymmetric bet: it won't hurt, but very well might help. It has been found to be effective in murine models.by marton78
- How old is your mother? Iirc PSEN1 correlates to very early AD, like late 30s early 40s. My dad had full blown AD at 65, with serious cognitive decline starting at 63, and that felt very early to us all. My dad had no AD biomarkers on full genetic scan. My heart goes out to you and your family.by nphardon
- Lithium, too! In mice. https://otd.harvard.edu/news/could-lithium-explain-and-treat...by adamredwoods
- Interestingly, lithium does seem to protect telomeres and in fact lengthens them, which may affect Alzheimer's.
- Great news! If you are a mouse.
For humans, not yet progressed to trials though safety has been evaluated for other diseases, so possible for trials to happen quickly?
" the compound has strong potential to quickly transition into human clinics because it has already undergone safety evaluations for other diseases."
by discretion22 - I mean why not allow right to try for people who are already so far gone. It can potentially help them and all of us.by PrincepsZero
- mice are having a great year
- The Hitchhiker's Guide was right. We spend all our time inventing new cures for the mice!by onraglanroad
- A genetically modified mouse with human amyloid-beta peptides. https://www.jax.org/strain/004462#by smallerize
- A lot of people here in the comments saying 'this can't work because amyloid beta hypothesis was wrong' seem to be missing that this treatment is aimed at some of the primary mediators of general brain health (function of natural BBB/vascular waste clearance mechanisms, which seem to degenerate over time, and modulation of neuroinflammation), not just clearing AB proteins pharmacologically. This jibes well with the stated improvements in Parkinsons and ALS.
I doubt there is one root cause of Alzheimers (except maybe in some genetic cases), and this is likely not a panacea, but sounds like it may assist some of the key processes involved in breakdown.
Root behaviors related to sleep quality and quantity, diet, exercise, infection, environmental exposure and stress, as well as genetics, likely all contribute.
But, waste clearing and neuro-inflammation seem to be core processes involved in the progression of the pathology, and improving natural vascular waste clearance seems like a logical place to find at least a small improvement in progression and symptoms...
Analogy: if someone puts metal shavings in an engine, having a better oil filter won't prevent all damage caused by the person putting the metal shavings there (nor will it halt the process), but it will reduce the damage by getting those shavings out of circulation before they have a chance to make even more repeated passes through the engine and do even more more damage. Improved vascular waste clearance is likely only a small piece of the puzzle, like having good oil pressure and filtration, but that doesn't mean it's irrelevant just because it doesn't prevent the other upstream root causes!
by layla5alive - I think people are reacting to the press-release more than the work.
I don't see why this is definitely doomed just because they discuss beta-amyloid plaques. Those exist and are real. They probably don't cause it any more than tombstones cause graveyards; very related, but not in the directly mechanistic way we wish.
> Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder characterized by the accumulation of amyloid-beta (Aβ) peptides in the brain.
This can be true and still not be the specific mechanism.
You can treat a specific waste product or you can repair the waste stream. The issue may be waste, but not a specific product, or the issue may not be the waste stream at all.
This work appears to demonstrate evidence of waste stream repair via a well-known waste-product. That doesn't mean that any specific waste product is or is not the problem or that this particular stream is definitely going to remove enough of the waste (if that was the problem).
Maybe there have been a lot of drugs which have similarly attempted waste-stream repair so there's good reason to doubt it on that alone. But I don't think that mentioning beta-amyloid plaque is enough to discard this out-of-hand.
by ebolyen - It is also worth mentioning that many of the alternative explanations involve brain infection, and improving brain/blood barrier also apply to that.by yxhuvud
- Alzheimer’s is driven by the buildup of toxic proteins called amyloid-beta.
In the words of Derek Lowe:
Amyloid-directed therapies truly, truly do not appear to be the answer for Alzheimer’s treatment. When I started work in the field back in the early 1990s, I was convinced of the opposite - the evidence looked very strong that defects in amyloid processing were indeed the cause of the disease. But that was thirty-five years ago, thirty-five years in which therapy after therapy after therapy aimed at amyloid mechanisms has failed.
[…] We’re way past persistence, way past focus, way past optimism and multiple shots on goal and old-college-tries. Do something else! For God's sake, do something else.
— https://www.science.org/content/blog-post/anti-amyloid-antib...
by quadhome - Having said that, this therapy could be improving clearing of all sorts of things, not just amyloid-beta. If amyloid is just a misleading side effect, clearing it could also be misleading.by pfdietz
- The podcast "Why Has There Been So Little Progress on Alzheimer’s Disease?" https://freakonomics.com/podcast/why-has-there-been-so-littl... discusses a lot of the academic fraud that lead to people following the Amyloid hypothesis.
The TLDR is that the researchers were publishing doctored images to support their hypothesises, which is why the Amyloid hypothesis was such a dead end.
by gwbas1c - If you read the actual article you will see this doesn't target the amyloid directly at all, but instead improve the brain/blood barrier and restore normal function of immune system, somehow.by yxhuvud
- I care what works, not about debate. This seems to work and that trumps any debate about what the real means are.
Don't get me wrong, if you are in this area of research this debate is important. There may be other types of Alzheimer's that have a different means. This drug may actually target something else. There might be some other truth I haven't thought it - but to me as an outsider the important part is a treatment that works, not why it works.
by bluGill - > Alzheimer’s is driven by the buildup of toxic proteins called amyloid-beta.
Isn't the current thinking that amyloid-beta buildup is a marker, not a cause? The therapy may be working here, but it isn't clear whether clearing amyloid-beta proteins is the mechanism or an outcome.
by dbcurtis - This is just one person's (informed I assume) opinion tough. It does sound like common sense but alas common sense is rarely a good guide when it comes down to how the body works.
I don't have a dog in this fight and I don't remember that much but I read someone's "in defense of the amyloid hypothesis" with interest. So if you want an counterpoint, you can go read https://www.astralcodexten.com/p/in-defense-of-the-amyloid-h...
by cassepipe