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> Within hours of the first injection, the animal brains showed a nearly 45 percent reduction in clumps of amyloid-beta plaques, a hallmark of Alzheimer's disease.

> The mice had previously shown signs of cognitive decline, but after all three doses, the animals performed on par with their healthy peers in spatial learning and memory tasks. The benefits lasted at least six months.

1. This is great news… for mice with Alzheimer’s that don’t mind treatments every 6 months.

2. It’s crazy to think about something like this actually curing Alzheimer’s in humans, even if for just 6 months. Even more so if repeated doses have the same effects.

3. As with all of these studies, mice != humans, but it’s nice to have hope.

Side note: the temporary part of #2 makes me think about The Last Days of Ptolemy Grey [1]. It’s hard to fathom having a relative “come back” like that for a short time. Or even permanently.

[1] https://www.imdb.com/title/tt13820498

8 comments

#2 reminds me more of *Flowers for Algernon"

This resonates with me particularly strongly, as one of the many failures of my body is that I live with NPH (normal pressure hydrocephalus).

Almost a week ago, I had a spinal tap as a diagnostic test to see if I truly had NPH or if there was a different reason for the bubble of fluid in my brain. An hour after the tap, I felt my arms and legs moving more freely than they had in years, and I was able to move significantly faster than before. And now, a week later, I can feel the stiffness setting in again. I'm sliding my feet more, and I can't move as quickly.

I don't know how to characterize the sense of loss I feel. As my body returns to the pre-spinal tap "normal." I'm left with the fading sensation of a freer movement and a clearer mind, with the hope that one of the treatments for NPH will restore that better self.

I can only imagine, with a bit of horror, the sense someone would have coming out of the fog of Alzheimer's, feeling normal for months. Then the anxiety one might feel, as the Alzheimer's fog returns, and be scared that it might not go away again with the next dose—a real "Flowers for Algernon" moment.

I still need to talk to my neurologist to find out if I qualify for the CFS shunt/drain operation. It would be nice to have a clearer mind and freer body, even if I do become part Borg.

fascinating post, thank you

If this was effective on humans I think most people would accept having treatments 2x a year

One must live a very privileged life to mind a 2x a year inconvenience in exchange for a working brain.

I wouldn't mind 10x a day injections if it keeps Alzheimer's at bay. Actually, I wouldn't mind a continuous IV drip.

I usually consider dialysis to be the point where treatments start to become very limiting. Twice a week, most people feel tied to their dialysis clinic and cannot go far from it.

Dialysis specifically requires several hours and a specific location and its debilitating. Going to a random pharmacy to take an injection 2x a week would be much simpler.

Being forced to sit in a chair for several hours every few days isn't what makes dialysis so debilitating. It's the loss of kidney function that dialysis doesn't replace, tied with the cardiovascular stress of emptying all the waste from the body at once.

And plenty of people living with diabetes manage to self-medicate with injections multiple times a day.

I have an acquaintance who has lived most of his life without kidneys(40 years). Looking in from the outside, his life seems normal; go to the gym and have a beer or two like anyone would, except for the dialysis trips.

I then have a relative into their late 60's that was very laxed about diabetics within recent years.This has lead to kidney issues. They are refusing dialysis because of I guess the stigma attached to it. Now they are experiencing a cognitive decline due to poorly functioning kidneys.

I guess when you want to live you would do whatever it takes.

Why has nobody made a backpack dialysis machine so you can keep going about your day?

It's not the size of a backpack but my wife did home hemo dialysis with a machine that had a handle and was portable. We even took it on trips a few times. I forget the weight, but, from memory, was around 10 pounds / 4.5 kg I think. Wife has had a transplant so my home hemo experience is from a few years ago. It may have changed since then.

The machine's portability wasn't the only factor. Needed a clean space to set up. There was a second machine hooked up to the house water lines. It would be used to create dialysate which was pumped into the dialysis machine. You could travel without the water pump, but to replace it, you needed these massive disposable bags of dialysate. Each bag was heavier than the machine itself and they were essential.

I guess with car trips, you could take the pump too to generate dialysate on site but it wasn't designed for portability as much as the main dialysis machine was. Was heavier. We kept it on rollers.

There were other supplies needed too. Saline bags. The dialysis machine had one-time use cartridges that were quite convenient but took up a fair bit of space. All added up to considerable bulk.

We only used the machine at distant locations when we knew we were going to be there for a week or more. One factor that made things a little easier was the the dialysis company was willing to deliver supplies to wherever we were, as long as it was within the US. We didn't have to take weeks worth of supplies. But we did have to take enough supplies to get through the first few days before delivery.

Vacations were rare but doable if we were going by car or if there was a dialysis center at the location. I guess we could have flown with the machine but we didn't trust airline baggage handlers enough to risk it.

There is peritoneal dialysis, which is pretty portable and doesn’t filter the blood (it exchanges peritoneal fluid, which is a lot less invasive). It’s actually quite fascinating how simple the machine is — and in fact, the simplest version of the machine is literally two bags and a couple of valves, completely operated by gravity. Everyone is not eligible for this type of dialysis, however. I don’t remember why.

Oh, also, if you do peritoneal dialysis, it’s daily, whereas hemo dialysis is generally two or three times a week.

> wouldn't mind 10x a day injections if it keeps Alzheimer's at bay. Actually, I wouldn't mind a continuous IV drip.

There seems to be a much better way:

https://publichealth.jhu.edu/2025/small-amounts-of-moderate-...

"The researchers found that engaging in as little as 35 minutes of moderate to vigorous physical activity per week, compared to zero minutes per week, was associated with a 41% lower risk of developing dementia over an average four-year follow-up period. Even for frail older adults—those at elevated risk of adverse health outcomes—greater activity was associated with lower dementia risks.

The researchers found dementia risk decreased with higher amounts of physical activity. Dementia risks were 60% lower in participants in the 35 to 69.9 minutes of physical activity/week category; 63% lower in the 70 to 139.9 minutes/week category; and 69% lower in the 140 and over minutes/week category."

People keep telling they'd sacrifice everyting for an hypothetical silver bullets while doing nothing in their day to day life to mitigate all these disease. Eat clean, exercise, 8 hours of deep good uninterrupted sleep, &c.

3/4th of people are obese or overweight, the average Joe walks like 4k steps a day, people, at large, don't give a shit about health until they get a terminal diagnosis

My father was very active well into his 80s, going for 10+km bike rides almost every day, until he got heart trouble. He would still walk for hours every day, often taking the stairs up the local hill, 400+ steps. He still got Alzheimer's. A lighter, later case than he would otherwise had, I'm sure, but still, he doesn't remember what he said 2 minutes ago, asking about the same things over and over again.

So while there are lots of excellent reasons to stay active into old age, it's not a replacement for treatment.

Apples and oranges.

You're talking about prevention, but this is about cure / treatment.

Once you have already have Alzheimer's, exercise isn't going to save you.

Doesn't fully correct for different biaises like healthy user bias so it proves association more than causality.

What am I to infer from this? That people prone to dementia tend to have less energy for voluntary vigorous physical activity?

If not, why not?

If it was effective on humans I think people would accept daily treatments, were it to be necessary - Alzheimer’s is just that awful.

The alternative is 24/7 care in a long-term care facility with multiple RCWs per floor and a couple of RNs. There are definitely enough Human Resources available to support this initiative.

Of course, but that’s assuming:

1. There aren’t serious side effects that make it more of a tradeoff

2. The price isn’t on the order of 6-7 figures (or possibly less for some)

As someone close to a severe Alzheimer’s case - I would personally write a check for $100K in a heartbeat for a treatment that worked.

And yes - I mean I would do that every 6 months.

I’m curious: Do you have any idea what care for such situations costs today?

I don’t, no.

But my point isn’t so much about willingness to pay for such a treatment, but ability to pay for such a treatment.

My understanding is that some treatments like this are sometimes not covered by insurance, so only high income individuals are able to afford them.

On the other hand, long-term care often is covered by insurance, and the insurance is more affordable.

Close to nothing if you live in a multi generational house where people are close by and can take care of each other, thousands per month if you delegate everything to medical practices. I've witnessed both cases, many times

#2 isn't necessarily so even. They said the effects lasted at least 6 months, not "only". I haven't read the study, but it sounds to me that it was 6 months of success then publish.

Yes, and consider how an animal that lives only 2 years gets Alzheimer's in the first place. They must be genetically engineered to have super turbo Alzheimer's. Normal Alzheimer's doesn't progress so fast I think.

This is a really important thing to keep in mind with these studies, we don't actually know that we're curing Alzheimer's in these mice. We don't even know if mice really get Alzheimer's in the way we do. What we're curing is mice who've been genetically modified to overproduce a protein that's associated with Alzheimer's, and we think that's a good model because the overproduction seems to cause symptoms that look like what Alzheimer's would look like in mice, but it's still just a model.

You DNRTFA. It explains that there are test strains of mice with a genetic condition that predisposes them to Alzheimer's-like conditions.

As always, there's no guarantee that it will work IRL on Homo sapiens.

Also, lab mice only live for ~2 years. A study of mice for significantly longer than that doesn't make sense.

I immediately thought of Awakenings https://en.wikipedia.org/wiki/Awakenings_(book) also.

The Last Days of Ptolemy Grey makes me think of Flowers for Algernon.

https://raio.org/FlowersForAlgernon.pdf

https://en.wikipedia.org/wiki/Flowers_for_Algernon

I don’t know why this isn’t a case where human subjects for the tests aren’t allowed.

Human trials may eventually be allowed, but I suspect that the results are preliminary and much work still needs to be done to assess the drug's safety before it makes it to humans.

Let me tell you a story about a biotech startup that I worked at many moons ago.

- We were trying to develop new antibiotics to treat certain bacterial infections.

- We had created a new antibiotic that was chemically similar to an existing, commercially successful antibiotic.

- But our drug was ~2-4× more potent at killing certain pathogenic bacteria than the existing med.

- Sounds good for us, right?

- Well, the commercially successful antibiotic was also toxic to humans if administered for "long" periods (it causes severe anemia if administered for 20+ days [I may not remember the precise details here]).

- Therefore, we were concerned that if our drug was 2-4× more potent at killing the microbes, it might also be 2-4× more toxic to people.

- To obtain approval for human tests, we had to run toxicity tests of our drug using several non-human species. Those results were mixed (toxic in some species, non-toxic in others), but we did eventually get approval.

- Unfortunately, the original concerns were correct: our drug caused severe anemia within ~3 days (again, specifics may be wrong), which means that particular candidate died in Phase 1 (initial human trial assessing drug safety).

Thankfully, the severe anemia was reversible in our test subjects (stop taking the drug, and the anemia went away)

You’re not seeing all the other candidate treatments that made things worse. If it just gives everyone a heart attack immediately the question would be, why didn’t you try this out on mice first?

My body, my choice. I get the restriction on marketing and selling until some degree of safety and perhaps efficacy is demonstrated. But I should be allowed to choose to take the treatment if offered for free, even without any previous study.

Human can’t consent in this case but they can feel immense pain and suffering still in ways that failed experimentation could invoke. Which may be worse than further decay and eventual death.

In many countries it's fairly easy to consent to euthanization. So these people could consent to participation in the study followed by immediate euthanization if the experiment fails and something worse than further decay awaits, no?

If the disease is severe enough to justify an untested treatment with unknown toxicity they aren't aware enough to grant consent.

True.

But they could give consent in advance.

If this horrific disease progresses to the point where ... I give my consent for ... Subject to final approval from family member/doctor/whatever.

>they aren't aware enough to grant consent

That's not really an obstacle, people in those situations have family members consent for all sorts of treatment already.

Because instead of curing their Alzheimer it might cause them to die faster with big side-effects if it's not tested well first.

Eventually they will be allowed and there will be a human trial. Not when they're still experimenting.

Just because someone has Alzheimer doesn't mean they're automatically a lab test subject.

This test shows effectiveness, they also need to go through trials to test for safety and unintended side effects

That’s actually the reverse order (and this trial didn’t test efficacy in humans).

>1. This is great news… for mice with Alzheimer’s that don’t mind treatments every 6 months.

Would you rather test it directly on humans?

Do you think they did it not caring whether it's also eventually applicable to humans all?

Do you think if the treatment reaches humans and is effective, and Alzheimer’s patient would "mind treatments every 6 months"?

It’s pretty clear that the commenter you’re responding to is making the point that a treatment effective in mice still has a long way to go before it’s viable for use on humans, assuming it is ever viable to use on humans.

Mice and humans are quite different, and whilst it looks like this treatment actually reverses the effects of dementia in mice, it’s far from clear that it would have the same impact on humans. By the time people start exhibiting Alzheimer’s symptoms, the brain will already have sustained quite a lot of damage - by which I mean death of neurons - so it’s hard to see how this would actually reverse the disease, as opposed to simply slowing or halting its progression, without these neurons being replaced.

Most people start exhibiting Alzheimer's symptoms long before they develop full-blown Alzheimer's. Starting treatment when a person has only taken a small amount of damage, reversing what would go on to cause further damage, could be a really big deal.

Aren't you a ray of sunshine...