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Copper transport drug restores memory and clears toxic Alzheimer's proteins

monash.edu

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Re: Copper transport drug restores memory and clears toxic Alzheimer's proteins

#71

Post by djdjkddkkd »

DavidSJ wrote: post #69
dekhn wrote: post #64

Earlier quoted context omitted.

My estimate of the quality of the evidence is based on daily discussions with people who work in that field and reading summary articles in major journals. I typically don't read raw scientific articles directly- those are aimed at people in the field. Instead, my understanding comes from a synthesis of expert opinions weighted by my own priors (based on 30+ years in the field). Derek's opinion is now the prevailing…

What started as an argument to ignore arguments and evidence and instead rely on authority, seems now to have morphed into an argument that we should ignore the authority of the establishment, because of your own personal assessment of the evidence (which you have not yourself read) and your own personal synthesis of conversations you've had with researchers you've personally come into contact with (despite this bein…

[dead]

Re: Copper transport drug restores memory and clears toxic Alzheimer's proteins

#72

Post by xenadu02 »

DavidSJ wrote: post #44
dekhn wrote: post #34

Earlier quoted context omitted.

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 in…

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.

Let's put all of that aside for a moment.

When the first drugs targeting HIV arrived the results were undeniable. Yes the drugs sucked for various reasons and yes HIV would evolve resistance. But the data demonstrated a very clear link that these drugs suppressed HIV and suppressing HIV made people live longer. Or consider mRNA and COVID, a great success story where the technology was put to good use and the results are obvious.

On the flip side we have certain cancers like certain breast cancers, melanoma, etc that never had a "wow" moment where some miracle turned them from highly fatal into treatable but we have seen decade after decade treatments improve and survival rates march ever upward such that what were once almost guaranteed death sentences are now often very treatable.

These are two disease treatment models worth keeping in mind. Sometimes major leaps are made. Sometimes progress is slow.

Now if we consider amyloid beta therapies: we have treatments that target amyloid beta with varying degrees of success but at least some show definite reductions in amyloid beta plaques. To the best of my knowledge that has not shown to improve outcomes in Alzheimer's patients to any meaningful degree.

That concerns me and I think justifies some skepticism of the amyloid hypothesis. The data is messy but if amyloid beta were a symptom not a cause that could certainly fit the results we are seeing. That doesn't mean the amyloid beta hypothesis is wrong but I think skepticism of the "state of the art" in the field is warranted given the pathetically ineffective progress made to date.

Re: Copper transport drug restores memory and clears toxic Alzheimer's proteins

#73

Post by [deleted] »

dbcurtis wrote: post #14
quadhome wrote: post #5

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-f…

> 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.

[deleted]

Re: Copper transport drug restores memory and clears toxic Alzheimer's proteins

#74

Post by anakaine »

projektfu wrote: post #16
vlovich123 wrote: post #9

Earlier quoted context omitted.

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…

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 appr…

In all fairness the cabal was only busted up in recent years, and it was largely responsible for ensuring that alternate lines of research could never get meaningful funding by denying publishing. So where the amyloid plaque line of researxh has had decades the alternate lines of research are only really getting enough sunlight to begin growing now.

The amyloid plaque cabal has quite likely sentenced tens if not hundreds of millions of people to premature death through their actions by preventing appropriate and alternative lines of research.

Re: Copper transport drug restores memory and clears toxic Alzheimer's proteins

#75

Post by kurthr »

DavidSJ wrote: post #56
dekhn wrote: post #54

Earlier quoted context omitted.

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 exp…

Wow, it sure didn't take long to show a complete lack of familiarity in the field. It seems like that's going to be a real weakness with LLMs based on volumes of material that are later discovered to be semi-fraudulent and unmotivated by scientific principals.

https://stanforddaily.com/2023/12/31/blockbuster-alzheimers-...

Re: Copper transport drug restores memory and clears toxic Alzheimer's proteins

#76

Post by cassepipe »

dekhn wrote: post #34
cassepipe wrote: post #23

Earlier quoted context omitted.

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-am…

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 in…

Fair enough but it's not by Scott Alexander but a guest post by David Schneider-Jospeh

EDIT: They edited their message to reflect that

Re: Copper transport drug restores memory and clears toxic Alzheimer's proteins

#77

Post by giantg2 »

cassepipe wrote: post #23
quadhome wrote: post #5

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-f…

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-am…

If I remember the studies right, removing the plaque doesn't reverse the dementia, and some drugs that show improvements in the dementia don't remove the plaque. There's clearly other stuff going on.

Re: Copper transport drug restores memory and clears toxic Alzheimer's proteins

#78

Post by DavidSJ »

kurthr wrote: post #75
DavidSJ wrote: post #56

Earlier quoted context omitted.

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 exp…

Wow, it sure didn't take long to show a complete lack of familiarity in the field. It seems like that's going to be a real weakness with LLMs based on volumes of material that are later discovered to be semi-fraudulent and unmotivated by scientific principals. https://stanforddaily.com/2023/12/31/blockbuster-alzheimers-...

As noted elsewhere in this thread, which you seem not to have read, I discuss that matter in the article, which you also seem not to have read.

Re: Copper transport drug restores memory and clears toxic Alzheimer's proteins

#79

Post by DavidSJ »

xenadu02 wrote: post #72
DavidSJ wrote: post #44

Earlier quoted context omitted.

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.

Let's put all of that aside for a moment. When the first drugs targeting HIV arrived the results were undeniable. Yes the drugs sucked for various reasons and yes HIV would evolve resistance. But the data demonstrated a very clear link that these drugs suppressed HIV and suppressing HIV made people live longer. Or consider mRNA and COVID, a great success story where the technology was put to good use and the results…

Now if we consider amyloid beta therapies: we have treatments that target amyloid beta with varying degrees of success but at least some show definite reductions in amyloid beta plaques. To the best of my knowledge that has not shown to improve outcomes in Alzheimer's patients to any meaningful degree.

This is false. They slow down disease progression by about 30%, as measured by cognitive outcomes. This is discussed in the article.

Re: Copper transport drug restores memory and clears toxic Alzheimer's proteins

#80

Post by markdown »

contingencies wrote: post #31
musiciangames wrote: post #20

Earlier quoted context omitted.

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…

> foreign students

FTFY. Not exchange students.

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