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.
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.
If I had to choose between Derek Lowe (author of the anti-amyloid-research article who is also highly experienced and skilled in pharma) and Scott Alexander/David Schneider-Joseph (psychiatrist and AI engineer, respectively), all my priors suggest Lowe gives better advice.
"I am David Schneider-Joseph, an engineer formerly with SpaceX and Google, now working in AI safety. Alzheimer’s isn’t my field, but I got very interested in it, spent six months studying the literature, and came away believing the amyloid hypothesis was basically completely solid. I thought I’d share that understanding with current skeptics."
6 months of reading literature when you don't know how to read biomedical literature isn't very confidence inducing. I know this site really likes it when smart outsiders come in and disrupt the status quo, but... probably not in this case.
This frequently comes up as a critique of my article, but I don't claim to be disrupting the field as a smart outsider. Rather, I looked at the field and concluded that the experts seem to know what they're doing. Derek Lowe is very much in the minority on this matter.
No, he's not (I work in pharma at a company that does basic and applied research on Alz). It's more correct to say there are several camps, but the camp promoting amyloid plaques as the causative/driver for Alz has struggled greatly to come up with evidence supporting its position.
Is your view that amyloid is actually a minority view among researchers? That seems completely wrong based on basically every conference proceeding I've viewed and the volume of papers and citations I've examined.
If your view is merely that there is a "camp" of experts that disagrees, then sure, but in that case, I do not think it is honest to frame this as a choice between believing in the authority of a single expert from that camp, vs. the (lack of) authority of me, a non-expert.
(I also think your read of the evidence is wrong, but I won't restate the arguments in my article.)
Is putting your thumb on the scale against Lowe. When a few replies down from here some commenters have provided an article demonstrating the exact fraudulent science in favor of what Lowe is saying.[0] It seems you may very well be disrupting it because he has a minority opinion. So you’ve possibly spent 6 months understanding an incorrect and fraud supported thesis. That seems like an outsider trying to disrupt it by using their “Google/SpaceX” creds to claim authority on the work of insiders.
1. I don't say Derek Lowe is wrong because he's in the minority. Minorities are sometimes right. But since the parent comment was arguing on authority and my lack thereof, I point out only that one shouldn't cherry-pick one's choice of authorities. Either accept the majority opinion of the experts, or come to your own opinion based on the quality of the arguments and evidence.
2. I would never want anyone to believe what I say because of "Google/SpaceX creds" (I didn't even write that line, Scott added it, and only to provide a brief biography and acknowledge that I do not work in the field, not to lend an air of authority to my words).
3. There's no need to cite the fraud to me, since I already discuss it in my article. You are welcome to read that article and form your own opinion about the arguments therein.
This really has become the new physics now, right where they think they can invade any given field in six months because that’s how long it’s supposed to take physicists to learn AI
In some ways physics is different from biology and medicine, I do think outsiders to physics can pick up and contribute a bit more easily (although it depends on field). Biomed just has an absolute insane amount of ambiguous knowledge that mostly gets picked up through diffusion across decades of learning. And many of the results in the literature are just wrong (one of the reasons I stopped being a researcher was seeing just how bad the publication record in biology is).
BTW, many physics people pick up the mechanical bits of machine learning/AI very quickly since they have all the foundational mathematics. The harder parts are understanding all the methods/tricks/complexity that got us to the state of the art- similar to biomed, you just sort of have to immerse yourself amongst knowledgeable people and let their knowledge diffuse in.
No actually there’s a large body of quashed research over these decades that went against the prevailing hypothesis. It’s one of the key examples of how peer review fails to consider novel approaches in the face of consensus even if consensus is shown to likely be wrong. The fact the original research driving the consensus was fraudulent at worst made it that much more sad.
To be clear this isn’t about whether it’s right or wrong it’s about that science involves investigating all avenues with evidence, proof, and rigor. Group think is how we end up incorporating bias into science, which is anti scientific.
Groupthink is very much the scientific method. According to Imre Lakatos the key question is does the group expand knowledge or contract it (very rushed reply as about to catch a flight)
In Lakatosian terms, the amyloid hypothesis is an example of a degenerating research program that has largely failed to predict new observations and is primarily driven by post hoc reasoning. The hypothesis was rescued by research claiming a significant new observation that was ultimately shown to be fraudulent (https://pmc.ncbi.nlm.nih.gov/articles/PMC12397490/).
From a Lakatosian perspective, the amyloid hypothesis is not necessarily wrong, but it is not paying off in terms of empirical insights relative to the amount of attention and funding it has received.
> Alzheimer’s isn’t my field, but I got very interested in it, spent six months studying the literature, and came away believing the amyloid hypothesis was basically completely solid.
If the accusation is "the field has been captured by a group with a vested interest in a model based on fraudulent research, strongly biasing what gets funded and what gets published" I wouldn't expect "studying the literature" to be particularly helpful in assessing the claim. It's sort of like saying "I read all of Enron's press releases and SEC filings, and they sound legit."
The defense reads more like a special pleading or sunk cost fallacy. There has been a lot of research done on one hypothesis, actively excluding alternatives,
so that hypothesis deserves to be considered until disproven (he does, iirc, allow for a test that would de-privilege the amaloyd hypothesis).
> 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.
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.
You are wrong. This paper very clearly does not show that it "works". The debate exists for a good reason - the very thing this paper claims to show is the exact thing the person you replied to was questioning. And that is a central question in all of Alzheimer's research.
There are dozens of studies that show mice improving their memory/spatial reasoning as Alzheimer's models. None of them have led to a proven improvement in longevity or quality of life for human Alzheimer's patients. Some of them slightly slow the progression, but even then you're getting into a gray area - is it really "better" to be stuck in the Alzheimer's fog for longer? Are we actually improving quality of life? It's unclear.
So no, in order for us to say that this approach "works", we would need randomized controlled clinical trials in humans showing a strict improvement in quality of life and/or longevity. This is not even close to that level of evidence.
In mice. This is a repeating trend in Alzheimer's research, where the amyloid-beta treatment works in the mouse model but not on humans, because the mouse model induces the amyloid-beta issue (mice don't really get Alzheimer's) and then we treat it.
The word "benefit" does not apply here. The only "benefits" patients and families care about are: 1) does the patient live longer, and/or 2) does the quality of life improve in a meaningful way? Amyloid plaques are a surrogate marker, and (as already explained by many people in this thread) have not been established as a causal factor in disease. In fact, some work has even suggested a protective role for plaques. So we do not have enough evidence to say that a 42% reduction in amyloid-beta IN MICE relays any benefit at all to humans.
You are correct that a series of clinical trials, which would take 7-10 years, would clear things up. But for now, we simply don't know.
I don’t think anyone is against a treatment that works, regardless of the mechanism.
The problem is that claimed success in these rat models has never transferred to humans. Either the problem is that rat Alzheimer’s is a poor model for human Alzheimer’s or the science being done is poor quality.
> Because reducing amyloid burden is clinically proven to improve functional outcomes, these preclinical results strongly support the rationale for testing this drug in early symptomatic Alzheimer’s disease
I believe this is the critical criticism of others. There’s now two camps. One side claims that the Amyloid movement is based on faulty science and outright fraud (true AFAIK) and the other side claims that there’s still evidence the amyloid hypothesis is accurate despite the flawed start to the hypothesis (possibly true). Generally I don’t trust a lot of effort being pushed behind a hypothesis that’s got such shady behavior from proponents and that rely on fast tracking drug approvals for drugs that reduce amyloids but clearly don’t benefit Alzheimer’s. Everyone gets to choose the priors they choose to evaluate the situation on.
If a beta-amyloid therapy eventually makes it to successful trials, there will still be people who believe the argument is already over and the therapy cannot work. The problem identified by Lowe and others is that some amyloid-oriented researchers were not only falsifying data but also acting as reviewers and editors of journals and tanking alternative explanations.
That has stopped, presumably, but alternative approaches haven't had much success yet either.
Therapies targeting amyloid deposits has been tested extensively in actual humans, and it indeed removes amyloid deposits. The main problem is that none of the therapies in question usefully treat Alzheimer’s disease.
Sure, maybe an eventual useful Alzheimer’s therapy will remove amyloid deposits, and maybe it won’t, but it needs to actually treat or at least meaningfully slow the actual disease.
In the title "....in the APP/PS1 Mouse Model of Alzheimer’s Disease"
Given the decades of emphasis on clearing / preventing amyloids I would be fairly jaded. If someone (biotech) wants to spend $$$ chasing this down, good on them.
But a paper curing a mouse model of a human neurological disease does not move the needle for someone with or watching someone suffer from this disease.
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.
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.
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.
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.
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.
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.
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.
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?
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.
Flagged. Nonsense puff piece by the university. The headline itself is beyond terrible - this is a mouse model and would need years of further successful research to be able to say that it "restores memory" in any meaningful way, let alone in actual humans.
The linked article is intentionally misleading by omission because they left out "in mice" in the university driven article and they certainly know the relevance and consequences of leaving it out.
AFAIK the background is the 'big 5' universities in Australia have a fat loan due which they took out 10 years ago and can't pay. Their primary income source was foreign exchange students and that demand has fallen off a cliff. So they're shedding academics and puffing like crazy right now. It seems in the near future Australian tertiary education will be highly corporatized and move to a more American model than our European-style history.
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
"Alzheimer’s is driven by the buildup of toxic proteins called amyloid-beta."
That's the predominant theory, but nothing affecting them has yet proven to be efficacious so far (AFAIK).
Likewise, at one time everyone "knew" aluminum was a culprit, because it showed up in autopsy analyses of affected people. However, it turned out that correlation wasn't from aluminum causing it, so avoiding aluminum didn't affect the disease.
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...
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...
If I had to choose between Derek Lowe (author of the anti-amyloid-research article who is also highly experienced and skilled in pharma) and Scott Alexander/David Schneider-Joseph (psychiatrist and AI engineer, respectively), all my priors suggest Lowe gives better advice.
"I am David Schneider-Joseph, an engineer formerly with SpaceX and Google, now working in AI safety. Alzheimer’s isn’t my field, but I got very interested in it, spent six months studying the literature, and came away believing the amyloid hypothesis was basically completely solid. I thought I’d share that understanding with current skeptics."
6 months of reading literature when you don't know how to read biomedical literature isn't very confidence inducing. I know this site really likes it when smart outsiders come in and disrupt the status quo, but... probably not in this case.
This frequently comes up as a critique of my article, but I don't claim to be disrupting the field as a smart outsider. Rather, I looked at the field and concluded that the experts seem to know what they're doing. Derek Lowe is very much in the minority on this matter.
No, he's not (I work in pharma at a company that does basic and applied research on Alz). It's more correct to say there are several camps, but the camp promoting amyloid plaques as the causative/driver for Alz has struggled greatly to come up with evidence supporting its position.
Is your view that amyloid is actually a minority view among researchers? That seems completely wrong based on basically every conference proceeding I've viewed and the volume of papers and citations I've examined.
If your view is merely that there is a "camp" of experts that disagrees, then sure, but in that case, I do not think it is honest to frame this as a choice between believing in the authority of a single expert from that camp, vs. the (lack of) authority of me, a non-expert.
(I also think your read of the evidence is wrong, but I won't restate the arguments in my article.)
“Derek Lowe is very much in the minority”
Is putting your thumb on the scale against Lowe. When a few replies down from here some commenters have provided an article demonstrating the exact fraudulent science in favor of what Lowe is saying.[0] It seems you may very well be disrupting it because he has a minority opinion. So you’ve possibly spent 6 months understanding an incorrect and fraud supported thesis. That seems like an outsider trying to disrupt it by using their “Google/SpaceX” creds to claim authority on the work of insiders.
[0] https://news.ycombinator.com/item?id=48544407
1. I don't say Derek Lowe is wrong because he's in the minority. Minorities are sometimes right. But since the parent comment was arguing on authority and my lack thereof, I point out only that one shouldn't cherry-pick one's choice of authorities. Either accept the majority opinion of the experts, or come to your own opinion based on the quality of the arguments and evidence.
2. I would never want anyone to believe what I say because of "Google/SpaceX creds" (I didn't even write that line, Scott added it, and only to provide a brief biography and acknowledge that I do not work in the field, not to lend an air of authority to my words).
3. There's no need to cite the fraud to me, since I already discuss it in my article. You are welcome to read that article and form your own opinion about the arguments therein.
This really has become the new physics now, right where they think they can invade any given field in six months because that’s how long it’s supposed to take physicists to learn AI
In some ways physics is different from biology and medicine, I do think outsiders to physics can pick up and contribute a bit more easily (although it depends on field). Biomed just has an absolute insane amount of ambiguous knowledge that mostly gets picked up through diffusion across decades of learning. And many of the results in the literature are just wrong (one of the reasons I stopped being a researcher was seeing just how bad the publication record in biology is).
BTW, many physics people pick up the mechanical bits of machine learning/AI very quickly since they have all the foundational mathematics. The harder parts are understanding all the methods/tricks/complexity that got us to the state of the art- similar to biomed, you just sort of have to immerse yourself amongst knowledgeable people and let their knowledge diffuse in.
I'm pretty sure there's an xkcd for this.
No actually there’s a large body of quashed research over these decades that went against the prevailing hypothesis. It’s one of the key examples of how peer review fails to consider novel approaches in the face of consensus even if consensus is shown to likely be wrong. The fact the original research driving the consensus was fraudulent at worst made it that much more sad.
To be clear this isn’t about whether it’s right or wrong it’s about that science involves investigating all avenues with evidence, proof, and rigor. Group think is how we end up incorporating bias into science, which is anti scientific.
I believe you don't have read the link I posted because its author does address the narrative you present here
But again I am not saying you are wrong and I am even sympathetic to this narrative but ultimately, unconvinced, either way
Groupthink is very much the scientific method. According to Imre Lakatos the key question is does the group expand knowledge or contract it (very rushed reply as about to catch a flight)
In Lakatosian terms, the amyloid hypothesis is an example of a degenerating research program that has largely failed to predict new observations and is primarily driven by post hoc reasoning. The hypothesis was rescued by research claiming a significant new observation that was ultimately shown to be fraudulent (https://pmc.ncbi.nlm.nih.gov/articles/PMC12397490/).
From a Lakatosian perspective, the amyloid hypothesis is not necessarily wrong, but it is not paying off in terms of empirical insights relative to the amount of attention and funding it has received.
Proofs and Refutations is a great book
https://a.co/d/0cXTgHgv
An example of fraud in research that contributed to the consensus.
> The 2006 paper suggested an amyloid beta (Aβ) protein called Aβ*56 could cause Alzheimer’s.
https://www.science.org/content/article/researchers-plan-ret...
> Alzheimer’s isn’t my field, but I got very interested in it, spent six months studying the literature, and came away believing the amyloid hypothesis was basically completely solid.
If the accusation is "the field has been captured by a group with a vested interest in a model based on fraudulent research, strongly biasing what gets funded and what gets published" I wouldn't expect "studying the literature" to be particularly helpful in assessing the claim. It's sort of like saying "I read all of Enron's press releases and SEC filings, and they sound legit."
The defense reads more like a special pleading or sunk cost fallacy. There has been a lot of research done on one hypothesis, actively excluding alternatives, so that hypothesis deserves to be considered until disproven (he does, iirc, allow for a test that would de-privilege the amaloyd hypothesis).
> 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.
Yes. And to anyone paying attention, this has been current since about 2010.
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.
You are wrong. This paper very clearly does not show that it "works". The debate exists for a good reason - the very thing this paper claims to show is the exact thing the person you replied to was questioning. And that is a central question in all of Alzheimer's research.
There are dozens of studies that show mice improving their memory/spatial reasoning as Alzheimer's models. None of them have led to a proven improvement in longevity or quality of life for human Alzheimer's patients. Some of them slightly slow the progression, but even then you're getting into a gray area - is it really "better" to be stuck in the Alzheimer's fog for longer? Are we actually improving quality of life? It's unclear.
So no, in order for us to say that this approach "works", we would need randomized controlled clinical trials in humans showing a strict improvement in quality of life and/or longevity. This is not even close to that level of evidence.
> Over 56 days, the treatment reduced toxic amyloid-beta by 42 per cent and improved spatial learning by nearly 44 per cent
So there's some benefit. Sounds like their next step is a much larger trial to answer the question you are posing.
https://pubs.acs.org/doi/10.1021/acschemneuro.6c00252
In mice. This is a repeating trend in Alzheimer's research, where the amyloid-beta treatment works in the mouse model but not on humans, because the mouse model induces the amyloid-beta issue (mice don't really get Alzheimer's) and then we treat it.
It is a repeating trend in all medical research. However enough does turn out to work in humans that we eventually make useful progress.
The word "benefit" does not apply here. The only "benefits" patients and families care about are: 1) does the patient live longer, and/or 2) does the quality of life improve in a meaningful way? Amyloid plaques are a surrogate marker, and (as already explained by many people in this thread) have not been established as a causal factor in disease. In fact, some work has even suggested a protective role for plaques. So we do not have enough evidence to say that a 42% reduction in amyloid-beta IN MICE relays any benefit at all to humans.
You are correct that a series of clinical trials, which would take 7-10 years, would clear things up. But for now, we simply don't know.
In fairness to parent, while the article doesn't say the title claims 'restores memories'.
I don’t think anyone is against a treatment that works, regardless of the mechanism.
The problem is that claimed success in these rat models has never transferred to humans. Either the problem is that rat Alzheimer’s is a poor model for human Alzheimer’s or the science being done is poor quality.
> Because reducing amyloid burden is clinically proven to improve functional outcomes, these preclinical results strongly support the rationale for testing this drug in early symptomatic Alzheimer’s disease
I believe this is the critical criticism of others. There’s now two camps. One side claims that the Amyloid movement is based on faulty science and outright fraud (true AFAIK) and the other side claims that there’s still evidence the amyloid hypothesis is accurate despite the flawed start to the hypothesis (possibly true). Generally I don’t trust a lot of effort being pushed behind a hypothesis that’s got such shady behavior from proponents and that rely on fast tracking drug approvals for drugs that reduce amyloids but clearly don’t benefit Alzheimer’s. Everyone gets to choose the priors they choose to evaluate the situation on.
If a beta-amyloid therapy eventually makes it to successful trials, there will still be people who believe the argument is already over and the therapy cannot work. The problem identified by Lowe and others is that some amyloid-oriented researchers were not only falsifying data but also acting as reviewers and editors of journals and tanking alternative explanations.
That has stopped, presumably, but alternative approaches haven't had much success yet either.
Therapies targeting amyloid deposits has been tested extensively in actual humans, and it indeed removes amyloid deposits. The main problem is that none of the therapies in question usefully treat Alzheimer’s disease.
Sure, maybe an eventual useful Alzheimer’s therapy will remove amyloid deposits, and maybe it won’t, but it needs to actually treat or at least meaningfully slow the actual disease.
In the title "....in the APP/PS1 Mouse Model of Alzheimer’s Disease"
Given the decades of emphasis on clearing / preventing amyloids I would be fairly jaded. If someone (biotech) wants to spend $$$ chasing this down, good on them.
But a paper curing a mouse model of a human neurological disease does not move the needle for someone with or watching someone suffer from this disease.
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.
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.
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."
A genetically modified mouse with human amyloid-beta peptides. https://www.jax.org/strain/004462#
mice are having a great year
The Hitchhiker's Guide was right. We spend all our time inventing new cures for the mice!
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.
Lithium, too! In mice. https://otd.harvard.edu/news/could-lithium-explain-and-treat...
Interestingly, lithium does seem to protect telomeres and in fact lengthens them, which may affect Alzheimer's.
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.
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.
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.
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.
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.
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?
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.
Flagged. Nonsense puff piece by the university. The headline itself is beyond terrible - this is a mouse model and would need years of further successful research to be able to say that it "restores memory" in any meaningful way, let alone in actual humans.
Press release should be replaced by actual journal article, which doesn’t omit “mouse model”.
The linked article is intentionally misleading by omission because they left out "in mice" in the university driven article and they certainly know the relevance and consequences of leaving it out.
Yes, it’s really disappointing to see Monash doing that - not a mention of mouse or mice.
AFAIK the background is the 'big 5' universities in Australia have a fat loan due which they took out 10 years ago and can't pay. Their primary income source was foreign exchange students and that demand has fallen off a cliff. So they're shedding academics and puffing like crazy right now. It seems in the near future Australian tertiary education will be highly corporatized and move to a more American model than our European-style history.
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)
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
https://pmc.ncbi.nlm.nih.gov/articles/PMC10052856/
Yep it's all AI-generated. It's annoying that they have a fake human as the author but whatever, it's the interslop.
"Alzheimer’s is driven by the buildup of toxic proteins called amyloid-beta."
That's the predominant theory, but nothing affecting them has yet proven to be efficacious so far (AFAIK).
Likewise, at one time everyone "knew" aluminum was a culprit, because it showed up in autopsy analyses of affected people. However, it turned out that correlation wasn't from aluminum causing it, so avoiding aluminum didn't affect the disease.
..in Mice