Could Lithium Explain — and Treat — Alzheimer’s Disease?

Miscellaneous and Personal Stuff I Must Share
1

There is some interesting research that was just published a couple weeks ago:

Could Lithium Explain — and Treat — Alzheimer’s Disease? Study: Lithium loss ignites Alzheimer’s, but lithium compound can reverse disease in mice

At a glance:

  • Study shows for the first time that lithium plays an essential role in normal brain function and can confer resistance to brain aging and Alzheimer’s disease.

  • Scientists discovered that lithium is depleted in the brain by binding to toxic amyloid plaques — revealing a new way Alzheimer’s may begin.

  • A new class of lithium-based compounds avoids plaque binding and reverses Alzheimer’s and brain aging in mice, without toxicity.

The open-access study itself was published in Nature:

Lithium deficiency and the onset of Alzheimer’s disease

https://www.nature.com/articles/s41586-025-09335-x

Some more articles:

Could lithium stave off Alzheimer’s disease?

https://www.science.org/content/article/could-lithium-stave-alzheimer-s-disease

I think a lot of us are more worried about getting Alzheimer’s and slowly losing our mind than from sudden death from a heart attack.

2

Yeah, I personally don’t fear death, but am absolutely terrified of any form of dementia.

3

I’m interested in seeing what happens during human trials. It may work fine in mice, but not in people.

4

Thirded.

Not every hopeful study turns out to produce a cure. But sometimes one does.

5

I heard a blurb about the study on the radio last week, so I looked up lithium orotate on Wikipedia. I was a bit surprised to learn that it was touted as an dementia treatment decades ago (since they didn’t mention that on the radio).

6

Here’s some learned commentary on this study by a med chem blogger I respect:
Lithium Deficiency and Alzheimer’s Disease | Science | AAAS.

7

Mice get Alzheimer’s? I’d have thought that only humans live long enough to even be able to get it.

8

That’s an encouraging article. Hope further research is done and that this will pan out.

9

I would guess it’s induced somehow. Maybe they implant amyloid plaques or twiddle a gene to accelerate it or something?

10

Or maybe they make the mice watch Matlock

11

Probably, but then that makes the question as to whether this is applicable to humans even stronger. How certain can they be that what they’re inducing in mice is actually similar to the human disease, or that the treatment isn’t just countering the inducement?

It’s definitely promising enough to justify further study, but study of Alzheimer’s in humans is very difficult. It can’t even be definitively diagnosed without an autopsy, which means that human studies can take decades.

12

That blogger I cited used to work directly on Alzheimer’s drug discovery. And it remains one of his personal interest areas. He’s written extensively on the topic, and has covered most of the significant announcements by other labs and drug companies as well.

If one is curious enough …

Here’s the category search for that oerve which currently yields 184 articles over 20+ years. That does include some articles by other authors; his current blog home doesn’t make it possible to filter by author. Alzheimer’s Disease | Science | AAAS.

13

Oh, yeah, folks definitely do research Alzheimer’s Disease in humans. It’s just really hard.

14

Here’s a followup blog post by my medchem blogger about the compound itself. Lithium Orotate Revisited | Science | AAAS.

It’s pretty chem-geeky, but might interest someone here.

15

Lithium supplement purveyors like to cite a few (scientifically invalid) studies where areas with naturally occurring lithium in the ground water have lower incidence of suicide.

This might be the next thing. I’ll believe it when I see the research. Until then, no different than vitamin C cures colds.

16

They use special lab breeds of mice that are susceptible to it, or an analog of AD. In this case, “3xTg AD mouse model, which accumulates Aβ deposits and phospho-tau, the J20 AD mouse model, which accumulates abundant Aβ deposits” versus “ageing wild-type mice without AD-type
pathology.”

17

Right, so what I’m wondering is whether that’s actually a close-enough analog. And to be fair, I’m sure all the researchers are wondering that, too. Biological research in general is difficult, and Alzheimer’s is a tough nut to crack even by biology standards.

Of course, it’s also possible that because of the differences between mice and humans, any given treatment might actually work better in humans with real Alzheimer’s than in mice with 3xTg AD.

18

There have been a lot of Alzheimers drugs successful in the mice–but virtually none successful in humans.

19

None actually. The one that got approved over the objections of every actual scientist was pure trumply graft at the top of the FDA.

20

There is more than one which has been approved.

The one you are talking about is Aducanumab (Aduhelm) which was highly controversial and later withdrawn from the market.

But there is another drug Lecanemab approved two years ago:

But it is expensive and requires frequent imaging (PET and MRI) for relatively modest benefits so has low usage.