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You are wrong. This paper very clearly does not show that it "works". The debate exists for a good reason - the very thing this paper claims to show is the exact thing the person you replied to was questioning. And that is a central question in all of Alzheimer's research.

There are dozens of studies that show mice improving their memory/spatial reasoning as Alzheimer's models. None of them have led to a proven improvement in longevity or quality of life for human Alzheimer's patients. Some of them slightly slow the progression, but even then you're getting into a gray area - is it really "better" to be stuck in the Alzheimer's fog for longer? Are we actually improving quality of life? It's unclear.

So no, in order for us to say that this approach "works", we would need randomized controlled clinical trials in humans showing a strict improvement in quality of life and/or longevity. This is not even close to that level of evidence.

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> Over 56 days, the treatment reduced toxic amyloid-beta by 42 per cent and improved spatial learning by nearly 44 per cent

So there's some benefit. Sounds like their next step is a much larger trial to answer the question you are posing.

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https://pubs.acs.org/doi/10.1021/acschemneuro.6c00252

In mice. This is a repeating trend in Alzheimer's research, where the amyloid-beta treatment works in the mouse model but not on humans, because the mouse model induces the amyloid-beta issue (mice don't really get Alzheimer's) and then we treat it.

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It is a repeating trend in all medical research. However enough does turn out to work in humans that we eventually make useful progress.
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In general, sure, but in this specific instance (treating Alzheimer's by clearing amyloid-beta) it's been shown over and over again to not work in humans.
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The word "benefit" does not apply here. The only "benefits" patients and families care about are: 1) does the patient live longer, and/or 2) does the quality of life improve in a meaningful way? Amyloid plaques are a surrogate marker, and (as already explained by many people in this thread) have not been established as a causal factor in disease. In fact, some work has even suggested a protective role for plaques. So we do not have enough evidence to say that a 42% reduction in amyloid-beta IN MICE relays any benefit at all to humans.

You are correct that a series of clinical trials, which would take 7-10 years, would clear things up. But for now, we simply don't know.

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In fairness to parent, while the article doesn't say the title claims 'restores memories'.
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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 support the rationale for testing this drug in early symptomatic Alzheimer’s disease

I believe this is the critical criticism of others. There’s now two camps. One side claims that the Amyloid movement is based on faulty science and outright fraud (true AFAIK) and the other side claims that there’s still evidence the amyloid hypothesis is accurate despite the flawed start to the hypothesis (possibly true). Generally I don’t trust a lot of effort being pushed behind a hypothesis that’s got such shady behavior from proponents and that rely on fast tracking drug approvals for drugs that reduce amyloids but clearly don’t benefit Alzheimer’s. Everyone gets to choose the priors they choose to evaluate the situation on.

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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 approaches haven't had much success yet either.

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Therapies targeting amyloid deposits has been tested extensively in actual humans, and it indeed removes amyloid deposits. The main problem is that none of the therapies in question usefully treat Alzheimer’s disease.

Sure, maybe an eventual useful Alzheimer’s therapy will remove amyloid deposits, and maybe it won’t, but it needs to actually treat or at least meaningfully slow the actual disease.

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In the title "....in the APP/PS1 Mouse Model of Alzheimer’s Disease"

Given the decades of emphasis on clearing / preventing amyloids I would be fairly jaded. If someone (biotech) wants to spend $$$ chasing this down, good on them.

But a paper curing a mouse model of a human neurological disease does not move the needle for someone with or watching someone suffer from this disease.

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> to me as an outsider the important part is a treatment that works, not why it works

Are you a mouse, perhaps? We have a plethora of treatments for mice suffering from human-induced Alzheimer's. None of those treatments have ever been shown to work for human patients, and this one is no different.

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