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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

#101

Post by amluto »

alliao wrote: post #83
helterskelter wrote: post #12

Earlier quoted context omitted.

Interestingly, lithium does seem to protect telomeres and in fact lengthens them, which may affect Alzheimer's.

interesting, I remember reading population of Beijing seem to have lithium in their water or air so their new born and mothers carrying seem to have 20x of lithium concentration of what's considered normal...

The papers suggest a plausible mechanism by which lithium orotate could have an effect that would be not present with inorganic lithium salts.

IIRC the hypothesis is that lithium orotate does not fully dissociate in water and thus can cross the blood brain barrier much more easily than plain Li+, and then the cells in your brain can take up the lithium orotate, metabolize the orotate part, and make the free Li+ available.

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

#102

Post by DaveZale »

pama wrote: post #95
DavidSJ wrote: post #79

Earlier quoted context omitted.

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…

I work in drug discovery. For the past twenty years or so, my personal analogy for this hypothesis has been a fantasy story around the days after the bombing of Dresden, when a new civilization suddenly visits Dresden and has no priors about what may have happened there. The aliens see bricks all over the place and assume that the bricks were the cause of the catastrophe. They take great efforts to pick up the bricks…

Yes, and the fact that something like oral hygiene can influence AD would support your thesis. Often an infection in the gums/teeth can result in boils or worse in distant parts of the body. Add a dysfunctional blood brain barrier and you are screwed.

Brush and floss bruddahs.

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

#103

Post by kurthr »

DavidSJ wrote: post #78
kurthr wrote: post #75

Earlier quoted context omitted.

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.

Not only have I read it, I know people mentioned in it. There aren't very many.

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

#104

Post by pas »

PrincepsZero wrote: post #40
discretion22 wrote: post #2

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."

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.

they can try it

simply this stuff was not even at that stage. it's a lab report. there's no company making it. though there's a version of this copper complex that targets ALS, and that is already available

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

#105

Post by stinkbeetle »

DavidSJ wrote: post #98
pama wrote: post #95

Earlier quoted context omitted.

I work in drug discovery. For the past twenty years or so, my personal analogy for this hypothesis has been a fantasy story around the days after the bombing of Dresden, when a new civilization suddenly visits Dresden and has no priors about what may have happened there. The aliens see bricks all over the place and assume that the bricks were the cause of the catastrophe. They take great efforts to pick up the bricks…

The hypothesis that amyloid is simply a downstream effect, not a cause, is of course worth considering, and where my mind was at when I first approached the literature skeptically. The widespread presence of amyloid-beta plaques in Alzheimer's disease has been known since 1906, but the field didn't adopt the amyloid hypothesis for decades precisely because of this possibility. But then in the early 1990's, strong gen…

Would you expect progression to cease if not reverse if the cause was cleared?

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

#106

Post by DavidSJ »

stinkbeetle wrote: post #105
DavidSJ wrote: post #98

Earlier quoted context omitted.

The hypothesis that amyloid is simply a downstream effect, not a cause, is of course worth considering, and where my mind was at when I first approached the literature skeptically. The widespread presence of amyloid-beta plaques in Alzheimer's disease has been known since 1906, but the field didn't adopt the amyloid hypothesis for decades precisely because of this possibility. But then in the early 1990's, strong gen…

Would you expect progression to cease if not reverse if the cause was cleared?

Not reverse; the neurons have died.

Cease, yes, if the cause is removed early enough. But if you intervene too late (once symptoms are detectable), then the downstream tau pathology, which is what directly kills neurons, likely spreads on its own via a prion-like mechanism.

So far, no clinical trial has completed prior to clinical onset for an antibody which actually removes plaque. This is probably the main reason only 30% slowdown has been achieved so far. The donanemab prevention trial is due to complete next year. That will be an important one to watch.

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

#107

Post by lmeyerov »

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…

I don't have a horse in this race, but for anyone who has worked in it, "science advances one funeral at a time" comes to mind here

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

#108

Post by yxhuvud »

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…

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.

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

#109

Post by yxhuvud »

ebolyen wrote: post #28

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 accumulati…

It is also worth mentioning that many of the alternative explanations involve brain infection, and improving brain/blood barrier also apply to that.

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

#110

Post by palmotea »

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…

> 6 months of reading literature when you don't know how to read biomedical literature isn't very confidence inducing.

Come on, he's a software engineer, a little reading will give him a shit-ton of confidence.

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