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Lithium compound can reverse Alzheimer’s in mice: study

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Re: Lithium compound can reverse Alzheimer’s in mice: study

#51

Watch out, there is no reliable Mouse Model for Alzheimer's. I was deeply involved with mouse models at some point before quitting my phd in neuroscience and I quite remember that.

Yes, but not only did they improve the memory of mouse models of Alzheimer's, they also improved the memory of older wild-type mice, which seems impressive to me. https://www.nature.com/articles/s41586-025-09335-x/figures/1...

Re: Lithium compound can reverse Alzheimer’s in mice: study

#52

Earlier quoted context omitted.

It's mostly the kidneys that get damaged, not so much the liver. It also has a massive amount of benign or merely annoying side effects. Lithium might even be the drug with the largest overall amount of side effects. It's certainly a weird one. High-dose lithium is extremely hard on your kidneys and may well lead to kidney failure in a decade or so. Medium-dose lithium is a lot more gentle but still requires monitori…

I have to say that I think the current popular idea of "we know how X drug works in the body because it does Y to Z" is patently insane. It may be useful information, sure, but it's not really _why_ it works, because we don't understand how the body works. It would be like Toyota saying: "the Corolla works on gasoline because it burns inside the engine, but we have no idea why the engine breaks when you put acetone i…

That monograph is not appropriate to this discussion because it is written for practitioners, not researchers. There is plenty of information on some of the things lithium is doing. My point was not "we have a complete understanding", but "we have some idea what is going on here, but there is still a lot we don't know".

Lithium is one of a large class of drugs that modulate the chemical potentials of the body's voltage-gated ion channels. There are a lot of drugs in this class, and most have been used with at least some degree of success to treat bipolar disorder. This class is also first-line treatment for many forms of epilepsy. The GABA system is directly tied in here too, and GABAergic agents are generally considered part of this class... and, guess what, they often help in bipolar as well. Lithium is a unique member of this class, and it is completely obvious (to a biochemist) that adding another species of alkali metal in sufficient concentration will disrupt the chemical potentials of sodium and potassium ion transport in the ion channels.

My point is: the first-level effect of lithium is well understood, and it affects an area that is well known to be affected by other drugs that have similar effects. So it is not total voodoo. However, you are also very correct that our understanding starts to break down after this. We can come up with new ion channel modulating drugs, and can reasonably expect them to be effective candidates for helping bipolar patients. What we cannot do is predict other targets or classes of drugs that might be interesting. That is where our understanding breaks down.

Re: Lithium compound can reverse Alzheimer’s in mice: study

#53
post #4

Lithium orotate is available over the counter. People could try it today. > Since lithium has not yet been shown to be safe or effective in protecting against neurodegeneration in humans, Yankner emphasizes that people should not take lithium compounds on their own I reject this kind of blind safetyism. A cursory search suggests that lithium orotate has been used for decades, and the article suggests that "profound e…

> I reject this kind of blind safetyism. You said you searched to learn more about lithium, but somehow missed that it's highly recommended to be administered by doctors due to side effects after long term use. Anything that damages your kidneys or thyroids can kill you, so calling it "blind safetyism" is silly.

>it's highly recommended to be administered by doctors due to side effects after long term use

This is at a clinical dose which is somewhat high. It is the dosage fund reliable as treatment for bipolar type 1. As long as you get your kidney numbers checked twice a year, at that dose, its mostly unproblematic as issues show themselves in the numbers before major damage.

Re: Lithium compound can reverse Alzheimer’s in mice: study

#54
post #2

Things I love to read. I went to visit my aunt one day, and my favourite uncle couldn't recognize me. It made me think that Alzheimer's is probably the worst thing that could happen to a person. I mean, what's worse than not being able to recognize those closest to you? You work a lifetime, and then you go out in such an undignified manner. I pray for a cure in my lifetime.

It's worse. Not recognizing people close to you is really hard on everyone else(including people taking care of you), but since you don't remember, it's not as bad for you. You won't even remember whether or not you had lunch. I met a grandma that was distraught that nobody was feeding her and she was hungry. Except she had had lunch already but couldn't remember. You forget where you live so if you get out of the ho…

What most people don't realize is that Alzheimer's - and its friend FTD - are terminal diseases with life expectancy just as bad as many cancers. Hardly anyone makes it to 5 years after diagnosis. The bodily degeneration that eventually results in the patient being utterly unable to function is heartbreaking. Forgetting things is a relatively minor symptom. It's also terrible on the family members of the patient whose mental health also suffers along the way.

Re: Lithium compound can reverse Alzheimer’s in mice: study

#55

Earlier quoted context omitted.

I have to say that I think the current popular idea of "we know how X drug works in the body because it does Y to Z" is patently insane. It may be useful information, sure, but it's not really _why_ it works, because we don't understand how the body works. It would be like Toyota saying: "the Corolla works on gasoline because it burns inside the engine, but we have no idea why the engine breaks when you put acetone i…

That monograph is not appropriate to this discussion because it is written for practitioners, not researchers. There is plenty of information on some of the things lithium is doing. My point was not "we have a complete understanding", but "we have some idea what is going on here, but there is still a lot we don't know". Lithium is one of a large class of drugs that modulate the chemical potentials of the body's volta…

I'm not sure why the relevant portion of the monograph isn't appropriate simply because of the target audience. "Alters sodium transport in nerve and muscle cells and effects a shift toward intraneuronal metabolism of catecholamines, but the specific biochemical mechanism of lithium action in mania is unknown" is the general consensus on lithium whether you're reading it as you, me, or Donald Duck.

Here is where we can both agree: we know a few things about the mechanism, which allow us to make some useful judgments in a few limited cases. We can also both agree that we know so little that, if a new, similar drug were proposed, with only a small change to its chemical structure, neither of us would dare make any confident statements about its action. We also cannot accurately predict what would happen if given to a patient with a well-studied but different disorder. In other words: most of the useful judgments about lithium - those that would be economically or socially interesting, for example - cannot be made from the model, because our understanding of the mechanism of action is too crude.

All of that is also, however, true about my hypothetical Corolla from my first example: we can say a few things, but most of the useful judgments that could be made from a full understanding cannot be made. It would be obvious to anyone that we do not understand the Corolla. So why, then, would we claim to understand lithium?

Re: Lithium compound can reverse Alzheimer’s in mice: study

#56
post #48

Watch out, there is no reliable Mouse Model for Alzheimer's. I was deeply involved with mouse models at some point before quitting my phd in neuroscience and I quite remember that.

Could you share some sources that show this to be true?

Not a source, but the fact that we can treat AD in mice but not humans should demonstrate OPs point sufficiently.

Re: Lithium compound can reverse Alzheimer’s in mice: study

#57
post #39

Earlier quoted context omitted.

I will ask you the same question I asked OP "Would you be willing to die of Alzheimer's in order to serve as a placebo for the control group? What about your parents?" Since that is essentially what you are asking the people that would have ordered low dose lithium based on this article to do.

Well I was the OP. It might be a tragedy of the commons situation. For each individual it may be better to ignore trials and just self medicate, but on the whole this could lead to an overall worse outcome in the long run.

Ha! you were op, my fault :)

Although that means you avoided answering my question directly multiple times although I think you strongly alluded that the answer would be no in your last response.

I look at my life and those of my family as precious and more valuable than all other lives (their lives over mine). I expect others to operate in a similar manner and that is why I am always taken aback at posts that seem to advocate for the sacrifice of one's self for the benefit of strangers. This is different of course from in the moment actions such as running into a burning building to save someone or stepping up to protect a woman you have never met from an aggressive man.

Your response while vague appears to indicate that you would not sacrifice yourself for this experiment either. Which is what I would expect from everyone.

I understand your general advocation for the clinical study and I agree with the need overall but not at the cost of intentionally sacrificing oneself.

So I'll pop a low dose lithium tablet along with a baby aspirin each night and hope you do the same. Wishing you a long life my friend.

Re: Lithium compound can reverse Alzheimer’s in mice: study

#58

Earlier quoted context omitted.

I've heard of suggestions that it should be added to water(in low doses of course) to see it reduces suicide rates. I like the idea but can only imagine the anti-flouride crowd would freak out.

I tried the low-dose lithium orotate supplements and the net effect was apathy and reduced motivation. Not everyone experiences this but from searching I’m not alone. Definitely not something to start pouring into the water supply.

That's exactly what the Lizard overlords are doing! /s - wouldn't be surprised there's a few conspiracy theorists who believe this...

Re: Lithium compound can reverse Alzheimer’s in mice: study

#59
post #48

Watch out, there is no reliable Mouse Model for Alzheimer's. I was deeply involved with mouse models at some point before quitting my phd in neuroscience and I quite remember that.

Could you share some sources that show this to be true?

Wild mice do not get AD. Even if you let them achieve old age they do not develop the same brain plaques or tangles that are linked to Alzheimers.

Even if they did you'd have to run huge samples then do post testing necropsies to see which mice had AD which which didn't, then filter your data, then try to find results in what remains.

Otherwise you can inject the mice with a chemical known to cause AD, which is not reliable on it's own, so you can get genetically modified mice which express _some_ of the known plaques and misfolds that are associated with human AD.

Animal testing is still, largely, a very unethical and cruel affair. AD testing in mice is especially fraught with hazard.

Re: Lithium compound can reverse Alzheimer’s in mice: study

#60
post #4

Lithium orotate is available over the counter. People could try it today. > Since lithium has not yet been shown to be safe or effective in protecting against neurodegeneration in humans, Yankner emphasizes that people should not take lithium compounds on their own I reject this kind of blind safetyism. A cursory search suggests that lithium orotate has been used for decades, and the article suggests that "profound e…

> I reject this kind of blind safetyism. You said you searched to learn more about lithium, but somehow missed that it's highly recommended to be administered by doctors due to side effects after long term use. Anything that damages your kidneys or thyroids can kill you, so calling it "blind safetyism" is silly.

When I started giving injections to a family member, I learned many things can cause problems that I didn't know about, such as that very tiny bits can break loose from the bottle top and cause issues. "Blind safetyism" is a point of view that can be more popular with certain personality types, but I think it's often a good starting point for research.
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